1  6890 229 [SCREENING, FUNCTIONAL ANALYSIS AND CLINICAL VALIDATION OF DIFFERENTIALLY EXPRESSED GENES IN DIABETIC FOOT ULCERS]. OBJECTIVE: TO SCREEN THE DIFFERENTIALLY EXPRESSED GENES (DEGS) IN DIABETIC FOOT ULCERS (DFUS), AND TO PERFORM FUNCTIONAL ANALYSIS AND CLINICAL VALIDATION OF THEM, INTENDING TO LAY A THEORETICAL FOUNDATION FOR EPIGENETIC THERAPY OF CHRONIC REFRACTORY WOUNDS. METHODS: AN OBSERVATIONAL STUDY WAS CONDUCTED. THE GENE EXPRESSION PROFILE DATASET GSE80178 OF DFU PATIENTS IN GENE EXPRESSION OMNIBUS (GEO) WAS SELECTED, AND THE DEG BETWEEN THREE NORMAL SKIN TISSUE SAMPLES AND SIX DFU TISSUE SAMPLES IN THE DATASET WAS ANALYZED AND SCREENED USING THE GEO2R TOOL. FOR THE SCREENED DEG, CLUSTERPROFILER, ORG.HS.EG.DB, GOPLOT, AND GGPLOT2 IN THE R LANGUAGE PACKAGES WERE USED FOR GENE ONTOLOGY (GO) ENRICHMENT ANALYSIS OF BIOLOGICAL PROCESSES, MOLECULAR FUNCTIONS, AND CELLULAR COMPONENTS, AND KYOTO ENCYCLOPEDIA OF GENES AND GENOMES (KEGG) ENRICHMENT ANALYSIS, RESPECTIVELY. PROTEIN-PROTEIN INTERACTION (PPI) ANALYSIS WAS PERFORMED USING STRING DATABASE TO SCREEN KEY GENES IN THE DEG, AND GO ENRICHMENT ANALYSIS OF KEY GENES WAS PERFORMED USING CYTOHUBBA PLUG-IN IN CYTOSCAPE 3.9.1 SOFTWARE. DFU TISSUE AND NORMAL SKIN TISSUE DISCARDED AFTER SURGERY WERE COLLECTED RESPECTIVELY FROM 15 DFU PATIENTS (7 MALES AND 8 FEMALES, AGED 55-87 YEARS) AND 15 ACUTE WOUND PATIENTS (6 MALES AND 9 FEMALES, AGED 8-52 YEARS) WHO WERE ADMITTED TO XIANG'AN HOSPITAL OF XIAMEN UNIVERSITY FROM SEPTEMBER 2018 TO MARCH 2021. THE MRNA AND PROTEIN EXPRESSIONS OF SMALL PROLINE-RICH REPEAT PROTEIN 1A (SPRR1A) AND LATE CORNIFIED ENVELOPE PROTEIN 3C (LCE3C) WERE DETECTED BY REAL-TIME FLUORESCENT QUANTITATIVE REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION AND IMMUNOHISTOCHEMISTRY, RESPECTIVELY. DATA WERE STATISTICALLY ANALYZED WITH INDEPENDENT SAMPLE T TEST. RESULTS: COMPARED WITH NORMAL SKIN TISSUE, 492 STATISTICALLY DIFFERENTIALLY EXPRESSED DEGS WERE SCREENED FROM DFU TISSUE OF DFU PATIENTS (CORRECTED P<0.05 OR CORRECTED P<0.01), INCLUDING 363 UP-REGULATED DEGS AND 129 DOWN-REGULATED DEGS. GO TERMINOLOGY ANALYSIS SHOWED THAT DEGS WERE SIGNIFICANTLY ENRICHED IN THE ASPECTS OF SKIN DEVELOPMENT, KERATINOCYTE (KC) DIFFERENTIATION, KERATINIZATION, EPIDERMAL DEVELOPMENT, AND EPIDERMAL CELL DIFFERENTIATION, ETC. (CORRECTED P VALUES ALL <0.01). KEGG PATHWAY ANALYSIS SHOWED THAT DEGS WERE SIGNIFICANTLY ENRICHED IN THE ASPECTS OF TUMOR-ASSOCIATED MICRORNA, RAS RELATED PROTEIN 1 SIGNALING PATHWAY, AND PLURIPOTENT STEM CELL REGULATORY SIGNALING PATHWAY, ETC. (CORRECTED P VALUES ALL <0.01). PPI ANALYSIS SHOWED THAT ENDOPHIAL PROTEIN, SPRR1A, SPRR1B, SPRR2B, SPRR2E, SPRR2F, LCE3C, LCE3E, KERATIN 16 (ALL DOWN-REGULATED DEGS), AND FILOPROTEIN (UP-REGULATED DEG) WERE KEY GENES OF DEGS SCREENED FROM DFU TISSUE OF DFU PATIENTS, WHICH WERE SIGNIFICANTLY ENRICHED IN GO TERMS OF KERATINIZATION, KC DIFFERENTIATION, EPIDERMAL CELL DIFFERENTIATION, SKIN DEVELOPMENT, EPIDERMIS DEVELOPMENT, AND PEPTIDE CROSS-LINKING, ETC. (CORRECTED P VALUES ALL <0.01). THE MRNA EXPRESSIONS OF SPRR1A AND LCE3C IN DFU TISSUE OF DFU PATIENTS WERE 0.588+/-0.082 AND 0.659+/-0.098, RESPECTIVELY, AND THE PROTEIN EXPRESSIONS WERE 0.22+/-0.05 AND 0.24+/-0.04, RESPECTIVELY, WHICH WERE SIGNIFICANTLY LOWER THAN 1.069+/-0.025 AND 1.053+/-0.044 (WITH T VALUES OF 20.91 AND 13.66, RESPECTIVELY, P VALUES ALL <0.01) AND 0.38+/-0.04 AND 0.45+/-0.05 (WITH T VALUES OF 9.69 AND 12.46, RESPECTIVELY, P VALUES ALL <0.01) IN NORMAL SKIN TISSUE OF ACUTE WOUND PATIENTS. CONCLUSIONS: COMPARED WITH NORMAL SKIN TISSUE, THERE IS DEG PROFILE IN DFU TISSUE OF DFU PATIENTS, WITH DEGS BEING SIGNIFICANTLY ENRICHED IN THE ASPECTS OF KC DIFFERENTIATION AND KERATIN FUNCTION. KEY DEGS ARE RELATED TO THE BIOLOGICAL FUNCTION OF KC, AND THEIR LOW EXPRESSIONS IN DFU TISSUE OF DFU PATIENTS MAY IMPEDE ULCER HEALING.	2022	

2  3501  54 IDENTIFICATION OF POTENTIAL BIOMARKERS FOR SYSTEMIC LUPUS ERYTHEMATOSUS BY INTEGRATED ANALYSIS OF GENE EXPRESSION AND METHYLATION DATA. INTRODUCTION: SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A HETEROGENEOUS AND CHRONIC AUTOIMMUNE DISEASE. ABERRANT DNA METHYLATION OCCURS DURING VARIOUS PROCESSES OF SLE DEVELOPMENT REGULATING THE MRNA EXPRESSION OF INTERRELATED GENES. THIS STUDY AIMS TO SCREEN POTENTIAL DNA METHYLATION MARKERS FOR SLE. METHODS: GENE EXPRESSION AND METHYLATION DATASETS WERE DOWNLOADED FROM THE GENE EXPRESSION OMNIBUS (GEO) DATABASE. DIFFERENTIALLY EXPRESSED GENES (DEGS) BETWEEN SLE PATIENTS AND HEALTHY CONTROLS WERE SCREENED USING THE LIMMA R PACKAGE, AND DIFFERENTIALLY METHYLATED POSITIONS (DMPS) AND REGIONS (DMRS) WERE IDENTIFIED USING DMPFINDER AND BUMPHUNTER (MINFI). ADDITIONALLY, THE DNA METHYLATION MARKERS TO DISTINGUISH SLE PATIENTS FROM HEALTHY CONTROLS WERE EXPLORED THROUGH RECEIVER OPERATING CHARACTERISTIC (ROC) CURVES AND LOGISTIC REGRESSION ANALYSES. FINALLY, WE VALIDATED THE RESULTS OF THE BIOINFORMATIC ANALYSIS BY PYROSEQUENCING. RESULTS: IN TOTAL, 91 DEGS, 90,092 DMPS, 15 DMRS, AND 13 DMR-ASSOCIATED GENES WERE IDENTIFIED. THROUGH THE INTEGRATIVE ANALYSIS OF DEG- AND DMR-ASSOCIATED GENES, WE IDENTIFIED FIVE TYPE I INTERFERON (IFN)-RELATED GENES AS KEY EPIGENETIC-DRIVEN GENES IN SLE. GO ENRICHMENT ANALYSIS SHOWED THAT THE FIVE SLE-ASSOCIATED EPIGENETIC-DRIVEN GENES WERE MAINLY ENRICHED IN THE TYPE I IFN SIGNALING PATHWAY INVOLVED IN IMMUNE RESPONSE AND DEFENSE RESPONSE TO VIRUS. MOREOVER, WE IDENTIFIED TWO SLE-SPECIFIC DNA METHYLATION MARKERS, THREE SLE WITHOUT LUPUS NEPHRITIS (SLE-LN(-))-SPECIFIC DNA METHYLATION MARKERS, AND TWO SLE WITH LUPUS NEPHRITIS (SLE-LN(+))-SPECIFIC DNA METHYLATION MARKERS BY STEPWISE LOGISTIC REGRESSION. CONCLUSIONS: OVERALL, OUR STUDY DEMONSTRATES POTENTIAL DNA METHYLATION MARKERS OF SLE, SLE-LN(-), AND SLE-LN(+), WHICH MAY HELP THE DIAGNOSIS, BOOST THE DEVELOPMENT OF NEW EPIGENETIC THERAPY, AND CONTRIBUTE TO INDIVIDUALIZED TREATMENT. KEY POINTS * THIS STUDY IDENTIFIED FIVE TYPE I IFN-RELATED GENES AS KEY EPIGENETIC-DRIVEN GENES IN SLE, WHICH SUPPORT THE IMPORTANCE OF THE TYPE I IFN PATHWAY IN THE PATHOGENESIS OF SLE * WE IDENTIFIED NOVEL DNA METHYLATION BIOMARKERS IN SLE, SLE-LN-, AND SLE-LN+ BY A COMPREHENSIVE ANALYSIS OF BIOINFORMATICS METHODS AND EXECUTED EXPERIMENTAL VALIDATION, AND BINARY LOGISTIC REGRESSION ANALYSIS SHOWED THAT THEY HAVE EXCELLENT POTENTIAL * THESE RESULTS MAY PROVIDE NEW INSIGHTS INTO THE BIOLOGICAL MECHANISMS OF SLE, AND IDENTIFY RELIABLE BIOMARKERS FOR SLE, SLE-LN-, AND SLE-LN+, WHICH MAY CONTRIBUTE TO DIAGNOSIS AND INDIVIDUALIZED TREATMENT.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
3   408  46 ANALYSIS OF GENE EXPRESSION AND METHYLATION DATASETS IDENTIFIED ADAMTS9, FKBP5, AND PFKBF3 AS BIOMARKERS FOR OSTEOARTHRITIS. BACKGROUND: OSTEOARTHRITIS (OA) IS A KIND OF CHRONIC OSTEOARTHROPATHY AND DEGENERATIVE JOINT DISEASE. EPIGENETIC REGULATION IN THE GENE EXPRESSION DYNAMICS HAS BECOME INCREASINGLY IMPORTANT IN OA. WE PERFORMED A COMBINED ANALYSIS OF TWO TYPES OF MICROARRAY DATASETS (GENE EXPRESSION AND DNA METHYLATION) TO IDENTIFY METHYLATION-BASED KEY BIOMARKERS TO PROVIDE A BETTER UNDERSTANDING OF MOLECULAR BIOLOGICAL MECHANISMS OF OA. METHODS: WE OBTAINED TWO EXPRESSION PROFILING DATASETS (GSE55235, GSE55457) AND ONE DNA METHYLATION PROFILING DATA SET (GSE63695) FROM THE GENE EXPRESSION OMNIBUS. FIRST, DIFFERENTIALLY EXPRESSED GENES (DEGS) BETWEEN PATIENTS WITH OA AND CONTROLS WERE IDENTIFIED USING THE LIMMA PACKAGE IN R(V3.4.4). THEN, FUNCTION ENRICHMENT ANALYSIS OF DEGS WAS PERFORMED USING A DAVID DATABASE. FOR DNA METHYLATION DATASETS, CHAMP METHYLATION ANALYSIS PACKAGE WAS USED TO IDENTIFY DIFFERENTIAL METHYLATION GENES (DMGS). FINALLY, A COMPREHENSIVE ANALYSIS OF DEGS AND DMGS WAS CONDUCTED TO IDENTIFY GENES THAT EXHIBITED DIFFERENTIAL EXPRESSION AND METHYLATION SIMULTANEOUSLY. RESULTS: WE IDENTIFIED 112 DEGS AND 2,896 DMGS IN PATIENTS WITH OA COMPARED WITH CONTROLS. FUNCTIONAL ANALYSIS OF DEGS OBTAINED THAT INFLAMMATORY RESPONSES, IMMUNE RESPONSES, AND POSITIVE REGULATION OF APOPTOSIS, TUMOR NECROSIS FACTOR (TNF) SIGNALING PATHWAY, AND OSTEOCLAST DIFFERENTIATION MAY BE INVOLVED IN THE PATHOGENESIS OF OA. CROSS-ANALYSIS REVEALED 26 GENES THAT EXHIBITED DIFFERENTIAL EXPRESSION AND METHYLATION IN OA. AMONG THEM, ADAMTS9, FKBP5, AND PFKBF3 WERE IDENTIFIED AS VALUABLE METHYLATION-BASED BIOMARKERS FOR OA. CONCLUSION: IN SUMMARY, OUR STUDY IDENTIFIED DIFFERENT MOLECULAR FEATURES BETWEEN PATIENTS WITH OA AND CONTROLS. THIS MAY PROVIDE NEW CLUES FOR CLARIFYING THE PATHOGENETIC MECHANISMS OF OA.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
4  6674  47 USE OF METHYLATION PROFILING TO IDENTIFY SIGNIFICANT DIFFERENTIALLY METHYLATED GENES IN BONE MARROW MESENCHYMAL STROMAL CELLS FROM ACUTE MYELOID LEUKEMIA. THE PRESENT STUDY AIMED TO CHARACTERIZE THE EPIGENETIC ARCHITECTURE BY STUDYING THE DNA METHYLATION SIGNATURE IN BONE MARROW MESENCHYMAL STEM CELLS (BM?MSCS) FROM PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML). MICROARRAY DATASET GSE79695 WAS DOWNLOADED FROM THE GENE EXPRESSION OMNIBUS DATABASE. DIFFERENTIALLY METHYLATED SITES AND DIFFERENTIALLY METHYLATED CPG ISLANDS WERE IDENTIFIED IN BM?MSC SAMPLES FROM PATIENTS WITH AML COMPARED WITH CONTROLS. MICRORNAS (MIRS) ENCODING GENES COVERING DIFFERENTIALLY METHYLATED SITES WERE FOUND AND THE REGULATION NETWORK WAS CONSTRUCTED. PATHWAY ENRICHMENT ANALYSIS OF HYPERMETHYLATED GENES AND HYPOMETHYLATED GENES WAS PERFORMED, FOLLOWED BY PROTEIN?PROTEIN INTERACTION (PPI) NETWORK CONSTRUCTION. MOREOVER, THE IDENTIFIED DIFFERENTIALLY METHYLATED GENES WERE COMPARED WITH THE LEUKEMIA?RELATED MARKER/THERAPEUTIC GENES FROM THE LITERATURE. OVERALL, 228 HYPERMETHYLATED CPG SITE PROBES COVERING 183 GENE SYMBOLS AND 523 HYPOMETHYLATED CPG SITES PROBES COVERING 362 GENE SYMBOLS WERE IDENTIFIED IN THE BM?MSCS FROM AML PATIENTS. FURTHERMORE, 4 GENES WITH CPG ISLAND HYPERMETHYLATION WERE IDENTIFIED, INCLUDING PEPTIDASE M20 DOMAIN CONTAINING 1 (PM20D1). THE HSA?MIR?596?ENCODING GENE MIR596 WAS FOUND TO BE HYPERMETHYLATED AND THE REGULATION NETWORK BASED ON HSA?MIR?596 AND ITS TARGETS (SUCH AS CYTOCHROME P450 FAMILY 1 SUBFAMILY B MEMBER 1) WAS CONSTRUCTED. HYPERMETHYLATED AND HYPOMETHYLATED GENES WERE ENRICHED IN DIFFERENT KYOTO ENCYCLOPEDIA OF GENES AND GENOMES PATHWAYS, INCLUDING 'HSA05221: ACUTE MYELOID LEUKEMIA' AND 'HSA05220: CHRONIC MYELOID LEUKEMIA', WHICH THE HYPOMETHYLATED GENE MITOGEN?ACTIVATED PROTEIN KINASE 3 (MAPK3) WAS INVOLVED IN. IN ADDITION, MAPK3, LYSINE DEMETHYLASE 2B AND RAP1A, MEMBER OF RAS ONCOGENE FAMILY WERE HUBS IN THE PPI NETWORK OF METHYLATED GENES. IN CONCLUSION, PM20D1 WITH HYPERMETHYLATION OF CPG ISLANDS MAY BE ASSOCIATED WITH THE ENERGY EXPENDITURE OF PATIENTS WITH AML. FURTHERMORE, THE ABERRANTLY HYPERMETHYLATED MIR?159?ENCODING GENE MIR159 MAY BE A POTENTIAL BIOMARKER OF AML.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
5  4868  57 OSTEOARTHRITIS RELATED EPIGENETIC VARIATIONS IN MIRNA EXPRESSION AND DNA METHYLATION. OSTEOARTHRITIS (OA) IS CHRONIC ARTHRITIS CHARACTERIZED BY ARTICULAR CARTILAGE DEGRADATION. HOWEVER, A COMPREHENSIVE REGULATORY NETWORK FOR OA-RELATED MICRORNAS AND DNA METHYLATION MODIFICATIONS HAS YET TO BE ESTABLISHED. THUS, WE AIMED TO IDENTIFY EPIGENETIC CHANGES IN MICRORNAS AND DNA METHYLATION AND ESTABLISH THE REGULATORY NETWORK BETWEEN MIRNAS AND DNA METHYLATION. THE MRNA, MIRNA, AND DNA METHYLATION EXPRESSION PROFILES OF HEALTHY OR OSTEOARTHRITIS ARTICULAR CARTILAGE SAMPLES WERE DOWNLOADED FROM GENE EXPRESSION OMNIBUS (GEO) DATABASE, INCLUDING GSE169077, GSE175961, AND GSE162484. THE DIFFERENTIALLY EXPRESSED GENES (DEGS), DIFFERENTIALLY EXPRESSED MIRNAS (DEMS), AND DIFFERENTIALLY METHYLATED GENES (DMGS) WERE ANALYZED BY THE ONLINE TOOL GEO2R. DAVID AND STRING DATABASES WERE APPLIED FOR FUNCTIONAL ENRICHMENT ANALYSIS AND PROTEIN-PROTEIN INTERACTION (PPI) NETWORK. POTENTIAL THERAPEUTIC COMPOUNDS FOR THE TREATMENT OF OA WERE IDENTIFIED BY CONNECTIVITY MAP (CMAP) ANALYSIS. A TOTAL OF 1424 UP-REGULATED DEGS, 1558 DOWN-REGULATED DEGS, 5 DEMS WITH HIGH EXPRESSION, 6 DEMS WITH LOW EXPRESSION, 1436 HYPERMETHYLATED GENES, AND 455 HYPOMETHYLATED GENES WERE SELECTED. A TOTAL OF 136 UP-REGULATED AND 65 DOWNREGULATED GENES WERE IDENTIFIED BY OVERLAPPING DEGS AND DEMS PREDICTED TARGET GENES WHICH WERE ENRICHED IN APOPTOSIS AND CIRCADIAN RHYTHM. A TOTAL OF 39 HYPOMETHYLATED AND 117 HYPERMETHYLATED GENES WERE OBTAINED BY OVERLAPPING DEGS AND DMGS, WHICH WERE ASSOCIATED WITH ECM RECEPTOR INTERACTIONS AND CELLULAR METABOLIC PROCESSES, CELL CONNECTIVITY, AND TRANSCRIPTION. MOREOVER, THE PPI NETWORK SHOWED COL5A1, COL6A1, LAMA4, T3GAL6A, AND TP53 WERE THE MOST CONNECTIVE PROTEINS. AFTER OVERLAPPING OF DEGS, DMGS AND DEMS PREDICTED TARGETED GENES, 4 UP-REGULATED GENES AND 11 DOWN-REGULATED GENES WERE ENRICHED IN THE AXON GUIDANCE PATHWAY. THE TOP TEN GENES RANKED BY PPI NETWORK CONNECTIVITY DEGREE IN THE UP-REGULATED AND DOWNREGULATED OVERLAPPING GENES OF DEGS AND DMGS WERE FURTHER ANALYZED BY THE CMAP DATABASE, AND NINE CHEMICALS WERE PREDICTED AS POTENTIAL DRUGS FOR THE TREATMENT OF OA. IN CONCLUSION, TP53, COL5A1, COL6A1, LAMA4, AND ST3GAL6 MAY PLAY IMPORTANT ROLES IN OA GENESIS AND DEVELOPMENT.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
6  1571  55 DNA METHYLATION PATTERNS IN CD8(+) T CELLS DISCERN PSORIASIS FROM PSORIATIC ARTHRITIS AND CORRELATE WITH CUTANEOUS DISEASE ACTIVITY. BACKGROUND: PSORIASIS IS A T CELL-MEDIATED CHRONIC AUTOIMMUNE/INFLAMMATORY DISEASE. WHILE SOME PATIENTS EXPERIENCE DISEASE LIMITED TO THE SKIN (SKIN PSORIASIS), OTHERS DEVELOP JOINT INVOLVEMENT (PSORIATIC ARTHRITIS; PSA). IN THE ABSENCE OF DISEASE- AND/OR OUTCOME-SPECIFIC BIOMARKERS, AND AS ARTHRITIS CAN PRECEDE SKIN MANIFESTATIONS, DIAGNOSTIC AND THERAPEUTIC DELAYS ARE COMMON AND CONTRIBUTE TO DISEASE BURDEN AND DAMAGE ACCRUAL. OBJECTIVE: ALTERED EPIGENETIC MARKS, INCLUDING DNA METHYLATION, CONTRIBUTE TO EFFECTOR T CELL PHENOTYPES AND ALTERED CYTOKINE EXPRESSION IN AUTOIMMUNE/INFLAMMATORY DISEASES. THIS PROJECT AIMED AT THE IDENTIFICATION OF DISEASE-/OUTCOME-SPECIFIC DNA METHYLATION SIGNATURES IN CD8(+) T CELLS FROM PATIENTS WITH PSORIASIS AND PSA AS COMPARED TO HEALTHY CONTROLS. METHOD: PERIPHERAL BLOOD CD8(+) T CELLS FROM NINE HEALTHY CONTROLS, 10 PSORIASIS, AND SEVEN PSA PATIENTS WERE COLLECTED TO ANALYZE DNA METHYLATION MARKS USING ILLUMINA HUMAN METHYLATION EPIC BEADCHIPS (>850,000 CPGS PER SAMPLE). BIOINFORMATIC ANALYSIS WAS PERFORMED USING R (MINFI, LIMMA, CHAMP, AND DMRCATE PACKAGES). RESULTS: DNA METHYLATION PROFILES IN CD8(+) T CELLS DIFFERENTIATE HEALTHY CONTROLS FROM PSORIASIS PATIENTS [397 DIFFERENTIALLY METHYLATED POSITIONS (DMPS); 9 DIFFERENTIALLY METHYLATED REGIONS (DMRS) WHEN >/=CPGS PER DMR WERE CONSIDERED; 2 DMRS FOR >/=10 CPGS]. FURTHERMORE, PATIENTS WITH SKIN PSORIASIS CAN BE DISCRIMINATED FROM PSA PATIENTS [1,861 DMPS, 20 DMRS (>/=5 CPGS PER REGION), 4 DMRS (>/=10 CPGS PER REGION)]. GENE ONTOLOGY (GO) ANALYSES CONSIDERING GENES WITH >/=1 DMP IN THEIR PROMOTER DELIVERED METHYLATION DEFECTS IN SKIN PSORIASIS AND PSA PRIMARILY AFFECTING THE BMP SIGNALING PATHWAY AND ENDOPEPTIDASE REGULATOR ACTIVITY, RESPECTIVELY. GO ANALYSIS OF GENES ASSOCIATED WITH DMRS BETWEEN SKIN PSORIASIS AND PSA DEMONSTRATED AN ENRICHMENT OF GABAERGIC NEURON AND CORTEX NEURON DEVELOPMENT PATHWAYS. TREATMENT WITH CYTOKINE BLOCKERS ASSOCIATED WITH DNA METHYLATION CHANGES [2,372 DMPS; 1,907 DMPS WITHIN PROMOTERS, 7 DMRS (>/=5 CPG PER REGIONS)] AFFECTING TRANSFORMING GROWTH FACTOR BETA RECEPTOR AND TRANSMEMBRANE RECEPTOR PROTEIN SERINE/THREONINE KINASE SIGNALING PATHWAYS. LASTLY, A METHYLATION SCORE INCLUDING TNF AND IL-17 PATHWAY ASSOCIATED DMPS INVERSE CORRELATES WITH SKIN DISEASE ACTIVITY SCORES (PASI). CONCLUSION: PATIENTS WITH SKIN PSORIASIS EXHIBIT DNA METHYLATION PATTERNS IN CD8(+) T CELLS THAT ALLOW DIFFERENTIATION FROM PSA PATIENTS AND HEALTHY INDIVIDUALS, AND REFLECT CLINICAL ACTIVITY OF SKIN DISEASE. THUS, DNA METHYLATION PROFILING PROMISES POTENTIAL AS DIAGNOSTIC AND PROGNOSTIC TOOL TO BE USED FOR MOLECULAR PATIENT STRATIFICATION TOWARD INDIVIDUALIZED TREATMENT.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
7   972  41 CHRONIC OBSTRUCTIVE PULMONARY DISEASE IS ASSOCIATED WITH EPIGENOME-WIDE DIFFERENTIAL METHYLATION IN BAL LUNG CELLS. DNA METHYLATION PATTERNS IN CHRONIC PULMONARY OBSTRUCTIVE DISEASE (COPD) MIGHT OFFER NEW INSIGHTS INTO DISEASE PATHOGENESIS. TO ASSESS METHYLATION PROFILES IN THE MAIN COPD TARGET ORGAN, WE PERFORMED AN EPIGENOME-WIDE ASSOCIATION STUDY ON BAL CELLS. BRONCHOSCOPIES WERE PERFORMED IN 18 SUBJECTS WITH COPD AND 15 CONTROL SUBJECTS (EX- AND CURRENT SMOKERS). DNA METHYLATION WAS MEASURED USING THE ILLUMINA METHYLATIONEPIC BEADCHIP KIT, COVERING MORE THAN 850,000 CPGS. DIFFERENTIALLY METHYLATED POSITIONS (DMPS) WERE EXAMINED FOR 1) ENRICHMENT IN PATHWAYS AND FUNCTIONAL GENE RELATIONSHIPS USING THE KYOTO ENCYCLOPEDIA OF GENES AND GENOMES AND GENE ONTOLOGY, 2) ACCELERATED AGING USING HORVATH'S EPIGENETIC CLOCK, 3) CORRELATION WITH GENE EXPRESSION, AND 4) COLOCALIZATION WITH GENETIC VARIATION. WE FOUND 1,155 BONFERRONI-SIGNIFICANT (P < 6.74 X 10(-8)) DMPS ASSOCIATED WITH COPD, MANY WITH LARGE EFFECT SIZES. FUNCTIONAL ANALYSIS IDENTIFIED BIOLOGICALLY PLAUSIBLE PATHWAYS AND GENE RELATIONSHIPS, INCLUDING ENRICHMENT FOR TRANSCRIPTION FACTOR ACTIVITY. STRONG CORRELATION WAS FOUND BETWEEN DNA METHYLATION AND CHRONOLOGICAL AGE BUT NOT BETWEEN COPD AND ACCELERATED AGING. FOR 79 UNIQUE DMPS, DNA METHYLATION CORRELATED SIGNIFICANTLY WITH GENE EXPRESSION IN BAL CELLS. THIRTY-NINE PERCENT OF DMPS WERE COLOCALIZED WITH COPD-ASSOCIATED SNPS. TO THE BEST OF OUR KNOWLEDGE, THIS IS THE FIRST EPIGENOME-WIDE ASSOCIATION STUDY OF COPD ON BAL CELLS, AND OUR ANALYSES REVEALED MANY DIFFERENTIAL METHYLATION SITES. INTEGRATION WITH MRNA DATA SHOWED A STRONG FUNCTIONAL READOUT FOR RELEVANT GENES, IDENTIFYING SITES WHERE DNA METHYLATION MIGHT DIRECTLY AFFECT EXPRESSION. ALMOST HALF OF DMPS WERE COLOCATED WITH SNPS IDENTIFIED IN PREVIOUS GENOME-WIDE ASSOCIATION STUDIES OF COPD, SUGGESTING JOINT GENETIC AND EPIGENETIC PATHWAYS RELATED TO DISEASE.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
8  3056  37 GENOME-WIDE DNA METHYLATION ANALYSIS IMPLICATES ENRICHMENT OF INTERFERON PATHWAY IN AFRICAN AMERICAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND EUROPEAN AMERICANS WITH LUPUS NEPHRITIS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC, MULTISYSTEM, INFLAMMATORY AUTOIMMUNE DISEASE THAT DISPROPORTIONATELY AFFECTS WOMEN. TRENDS IN SLE PREVALENCE AND CLINICAL COURSE DIFFER BY ANCESTRY, WITH THOSE OF AFRICAN AMERICAN ANCESTRY PRESENTING WITH MORE ACTIVE, SEVERE AND RAPIDLY PROGRESSIVE DISEASE THAN EUROPEAN AMERICANS. PREVIOUS RESEARCH ESTABLISHED ALTERED EPIGENETIC SIGNATURES IN SLE PATIENTS COMPARED TO CONTROLS. HOWEVER, THE CONTRIBUTION OF ABERRANT DNA METHYLATION (DNAM) TO THE RISK OF SLE BY ANCESTRY AND DIFFERENCES AMONG PATIENTS WITH SLE-ASSOCIATED LUPUS NEPHRITIS (LN) HAS NOT BEEN WELL DESCRIBED. WE EVALUATED THE DNA METHYLOMES OF 87 INDIVIDUALS INCLUDING 41 SLE PATIENTS, WITH AND WITHOUT LN, AND 46 CONTROLS ENROLLED IN AN ANCESTRY DIVERSE, WELL-CHARACTERIZED COHORT STUDY OF ESTABLISHED SLE (41 SLE PATIENTS [20 SLE-LN+, 21 SLE-LN-] AND 46 SEX-, RACE- AND AGE-MATCHED CONTROLS; 55% AFRICAN AMERICAN, 45% EUROPEAN AMERICAN). PARTICIPANTS WERE GENOTYPED USING THE INFINIUM GLOBAL DIVERSITY ARRAY (GDA), AND GENETIC ANCESTRY WAS ESTIMATED USING PRINCIPAL COMPONENTS. GENOME-WIDE DNA METHYLATION WAS INITIALLY MEASURED USING THE ILLUMINA METHYLATIONEPIC 850K BEADCHIP ARRAY FOLLOWED BY METHYLATION-SPECIFIC QPCR TO VALIDATE THE METHYLATION STATUS AT PUTATIVE LOCI. DIFFERENTIALLY METHYLATED POSITIONS (DMP) WERE IDENTIFIED USING A CASE-CONTROL APPROACH ADJUSTED FOR ANCESTRY. WE IDENTIFIED A TOTAL OF 51 DMPS IN CPGS AMONG SLE PATIENTS COMPARED TO CONTROLS. GENES PROXIMAL TO THESE CPGS WERE HIGHLY ENRICHED FOR INVOLVEMENT IN TYPE I INTERFERON SIGNALING. DMPS AMONG EUROPEAN AMERICAN SLE PATIENTS WITH LN WERE SIMILAR TO AFRICAN AMERICAN SLE PATIENTS WITH AND WITHOUT LN. OUR FINDINGS WERE VALIDATED USING AN ORTHOGONAL, METHYL-SPECIFIC PCR FOR THREE SLE-ASSOCIATED DMPS NEAR OR PROXIMAL TO MX1, USP18, AND IFITM1. OUR STUDY CONFIRMS PREVIOUS REPORTS THAT DMPS IN CPGS ASSOCIATED WITH SLE ARE ENRICHED IN TYPE I INTERFERON GENES. HOWEVER, WE SHOW THAT EUROPEAN AMERICAN SLE PATIENTS WITH LN HAVE SIMILAR DNAM PATTERNS TO AFRICAN AMERICAN SLE PATIENTS IRRESPECTIVE OF LN, SUGGESTING THAT ABERRANT DNAM ALTERS ACTIVITY OF TYPE I INTERFERON PATHWAY LEADING TO MORE SEVERE DISEASE INDEPENDENT OF ANCESTRY.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
9  3070  48 GENOME-WIDE DNA METHYLATION PROFILING IN CD8 T-CELLS AND GAMMA DELTA T-CELLS OF ASIAN INDIAN PATIENTS WITH TAKAYASU ARTERITIS. BACKGROUND: TAKAYASU'S ARTERITIS (TA) IS A CHRONIC INFLAMMATORY DISEASE THAT AFFECTS AORTA AND ITS MAIN BRANCHES AT THEIR ORIGIN. GENETIC, PATHOLOGICAL AND FUNCTIONAL STUDIES HAVE SHOWN THAT CD8 AND GAMMA DELTA (GAMMA/DELTA) T-LYMPHOCYTES ARE INVOLVED IN INFLAMMATORY PROCESSES IN AFFECTED REGIONS OF ARTERIES CAUSING VASCULAR DAMAGE. THE MOLECULAR FUNCTION OF THESE LYMPHOCYTES REMAINS UNCLEAR AND CURRENTLY NO EPIGENETIC STUDIES ARE AVAILABLE IN TA. WE PRIMARILY PERFORMED GENOME WIDE METHYLATION ANALYSIS IN CD8 T CELLS AND GAMMADELTA T CELLS OF PATIENTS WITH TA AND COMPARED WITH HEALTHY CONTROLS. METHODS: WE RECRUITED 12 SUBJECTS IN EACH GROUP NAMELY TA PATIENT AND HEALTHY CONTROLS. BLOOD SAMPLES WERE COLLECTED AFTER OBTAINING INFORMED WRITTEN CONSENT. CD8 T CELLS AND GAMMADELTA T CELLS WERE SEPARATED FROM WHOLE BLOOD. DNA EXTRACTED FROM THESE CELLS AND WERE SUBJECTED TO BISULFITE TREATMENT. FINALLY, BISULFITE TREATED DNA WAS LOADED IN INFINIUM METHYLATION EPIC ARRAY. BIOINFORMATICS ANALYSIS WAS USED TO IDENTIFY DIFFERENTIAL METHYLATION REGIONS WHICH WERE THEN MAPPED TO GENES. RESULTS: INTERLEUKIN (IL)-32 AND LYMPHOTOXIN-A WERE GENES SIGNIFICANTLY HYPOMETHYLATED IN CD8 T-CELLS. ANTI-INFLAMMATORY CYTOKINE GENES, IL-10, IL-1RN AND IL-27 WERE HYPOMETHYLATED IN GAMMADELTA T CELLS OF TA PATIENTS AS COMPARED TO HEALTHY CONTROLS. GENE ENRICHMENT ANALYSIS USING GENE ONTOLOGY (GO) DATABASE AND KYOTO ENCYCLOPAEDIA OF GENES AND GENOMES (KEGG) IDENTIFIED THAT GENES INVOLVED IN T-CELL RECEPTOR SIGNALLING PATHWAYS WERE HYPOMETHYLATED IN CD8 T-CELLS AND HYPERMETHYLATED IN GAMMADELTA T CELLS OF TA PATIENTS. CONCLUSION: CD8 T-CELLS MIGHT PLAY A MAJOR ROLE IN IMMUNOPATHOGENESIS OF INFLAMMATION IN TA, WHEREAS GAMMADELTA T CELLS MAY PLAY A REGULATORY ROLE.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
10   401  39 ANALYSIS OF ABERRANT METHYLATION ON PROMOTER SEQUENCES OF TUMOR SUPPRESSOR GENES AND TOTAL DNA IN SPUTUM SAMPLES: A PROMISING TOOL FOR EARLY DETECTION OF COPD AND LUNG CANCER IN SMOKERS. BACKGROUND: CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A DISORDER ASSOCIATED TO CIGARETTE SMOKE AND LUNG CANCER (LC). SINCE EPIGENETIC CHANGES IN ONCOGENES AND TUMOR SUPPRESSOR GENES (TSGS) ARE CLEARLY IMPORTANT IN THE DEVELOPMENT OF LC. IN THIS STUDY, WE HYPOTHESIZE THAT TOBACCO SMOKERS ARE SUSCEPTIBLE FOR METHYLATION IN THE PROMOTER REGION OF TSGS IN AIRWAY EPITHELIAL CELLS WHEN COMPARED WITH NON-SMOKER SUBJECTS. THE PURPOSE OF THIS STUDY WAS TO INVESTIGATE THE USEFULNESS OF DETECTION OF GENES PROMOTER METHYLATION IN SPUTUM SPECIMENS, AS A COMPLEMENTARY TOOL TO IDENTIFY LC BIOMARKERS AMONG SMOKERS WITH EARLY COPD. METHODS: WE DETERMINED THE AMOUNT OF DNA IN INDUCED SPUTUM FROM PATIENTS WITH COPD (N = 23), LC (N = 26), AS WELL AS IN HEALTHY SUBJECTS (CTR) (N = 33), USING A COMMERCIAL KIT FOR DNA PURIFICATION, FOLLOWED BY ABSORBANCE MEASUREMENT AT 260 NM. THE FREQUENCY OF CDKN2A, CDH1 AND MGMT PROMOTER METHYLATION IN THE SAME GROUPS WAS DETERMINED BY METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION (MSP). THE FISHER'S EXACT TEST WAS EMPLOYED TO COMPARE FREQUENCY OF RESULTS BETWEEN DIFFERENT GROUPS. RESULTS: DNA CONCENTRATION WAS 7.4 AND 5.8 TIMES HIGHER IN LC AND COPD COMPARED TO THE (CTR) (P < 0.0001), RESPECTIVELY. METHYLATION STATUS OF CDKN2A AND MGMT WAS SIGNIFICANTLY HIGHER IN COPD AND LC PATIENTS COMPARED WITH CTR GROUP (P < 0.0001). FREQUENCY OF CDH1 METHYLATION ONLY SHOWED A STATISTICALLY SIGNIFICANT DIFFERENCE BETWEEN LC PATIENTS AND CTR GROUP (P < 0.05). CONCLUSIONS: WE PROVIDE EVIDENCE THAT ABERRANT METHYLATION OF TSGS IN SAMPLES OF INDUCED SPUTUM IS A USEFUL TOOL FOR EARLY DIAGNOSTIC OF LUNG DISEASES (LC AND COPD) IN SMOKER SUBJECTS. VIRTUAL SLIDES: THE ABSTRACT MUST FINISH WITH THE FOLLOWING TEXT: VIRTUAL SLIDES THE VIRTUAL SLIDE(S) FOR THIS ARTICLE CAN BE FOUND HERE: HTTP://WWW.DIAGNOSTICPATHOLOGY.DIAGNOMX.EU/VS/1127865005664160.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
11  3460  37 HYPOMETHYLATION OF THE IL8 PROMOTER IN NASAL EPITHELIAL CELLS OF PATIENTS WITH CHRONIC RHINOSINUSITIS WITH NASAL POLYPS. BACKGROUND: IL-8 IS AN IMPORTANT CHEMOKINE IMPLICATED IN THE PATHOGENESIS OF CHRONIC RHINOSINUSITIS (CRS), BUT LITTLE IS KNOWN ABOUT EPIGENETIC REGULATION OF IL8 IN THE PATHOGENESIS OF CRS. OBJECTIVE: WE SOUGHT TO INVESTIGATE THE RELATIONSHIP BETWEEN THE DNA METHYLATION LEVEL IN THE IL8 PROXIMAL PROMOTER AND CRS IN HAN CHINESE SUBJECTS. METHODS: PATIENTS WITH CHRONIC RHINOSINUSITIS WITH NASAL POLYPS (CRSWNP; N = 187), PATIENTS WITH CHRONIC RHINOSINUSITIS WITHOUT NASAL POLYPS (CRSSNP; N = 89), AND CONTROL SUBJECTS (N = 57) WERE ENROLLED IN 2 INDEPENDENT COHORTS. PURIFIED HUMAN NASAL EPITHELIAL CELLS FROM EACH PARTICIPANT WERE ASSESSED FOR PERCENTAGE DNA METHYLATION OF CPG SITES IN THE IL8 PROXIMAL PROMOTER BY USING BISULFITE PYROSEQUENCING AND FOR FUNCTIONAL ASPECTS OF METHYLATION STATUS BY USING IN VITRO ASSAYS. RESULTS: DNA METHYLATION OF CPG SITES 1, 2, AND 3, RESPECTIVELY, IN THE IL8 PROXIMAL PROMOTER WAS SIGNIFICANTLY DECREASED IN HUMAN NASAL EPITHELIAL CELLS OF PATIENTS WITH CRSWNP COMPARED WITH THAT IN PATIENTS WITH CRSSNP (P < .001) AND CONTROL SUBJECTS (P < .001). PERCENTAGE OF DNA METHYLATION OF THE CPG3 SITE WAS CORRELATED NEGATIVELY WITH BOTH TISSUE EOSINOPHILIC CATIONIC PROTEIN (P < .01) AND MYELOPEROXIDASE (P < .05) LEVELS. IL-1BETA (P < .001) AND TNF-ALPHA (P < .01) SIGNIFICANTLY INCREASED IL8 EXPRESSION ACCOMPANIED BY A REDUCTION IN METHYLATION AT THE CPG3 SITE (P < .001). ELECTROPHORETIC MOBILITY SHIFT ASSAYS DEMONSTRATED THAT METHYLATION STATUS OF CPG3 CHANGED THE BINDING OF OCTAMER-BINDING TRANSCRIPTION FACTOR 1 AND NUCLEAR FACTOR KAPPAB. CONCLUSION: DECREASED DNA METHYLATION OF PARTICULARLY CPG SITES IN THE IL8 PROXIMAL PROMOTER MIGHT PLAY A ROLE IN THE PATHOGENESIS OF CRSWNP.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
12  1910  48 ENRICHMENT OF GENOMIC PATHWAYS BASED ON DIFFERENTIAL DNA METHYLATION PROFILES ASSOCIATED WITH KNEE OSTEOARTHRITIS PAIN. OUR STUDY AIMED TO IDENTIFY DIFFERENTIALLY METHYLATED REGIONS (I.E., GENOMIC REGION WHERE MULTIPLE ADJACENT CPG SITES SHOW DIFFERENTIAL METHYLATION) AND THEIR ENRICHED GENOMIC PATHWAYS ASSOCIATED WITH KNEE OSTEOARTHRITIS PAIN (KOA). WE RECRUITED COGNITIVELY HEALTHY MIDDLE TO OLDER AGED (AGE 45-85) ADULTS WITH (N = 182) AND WITHOUT (N = 31) SELF-REPORTED KOA PAIN. WE ALSO EXTRACTED DNA FROM PERIPHERAL BLOOD THAT WAS ANALYZED USING METHYLATIONEPIC ARRAYS. THE R PACKAGE MINFI (ARYEE ET AL., 2014) WAS USED TO PERFORM METHYLATION DATA PREPROCESSING AND QUALITY CONTROL. TO INVESTIGATE BIOLOGICAL PATHWAYS IMPACTED BY DIFFERENTIAL METHYLATION, WE PERFORMED PATHWAY ENRICHMENT ANALYSIS USING INGENUITY PATHWAY ANALYSIS (IPA) TO IDENTIFY CANONICAL PATHWAYS AND UPSTREAM REGULATORS. ANNOTATED GENES WITHIN +/- 5 KB OF THE PUTATIVE DIFFERENTIALLY METHYLATED REGIONS (DMRS, P < 0.05) WERE SUBJECTED TO THE IPA ANALYSIS. THERE WAS NO SIGNIFICANT DIFFERENCE IN AGE, SEX, STUDY SITE BETWEEN NO PAIN AND PAIN GROUP (P > 0.05). NON-HISPANIC BLACK INDIVIDUALS WERE OVERREPRESENTED IN THE PAIN GROUP (P = 0.003). AT RAW P < 0.05 CUTOFF, WE IDENTIFIED A TOTAL OF 19,710 CPG PROBES, INCLUDING 13,951 HYPERMETHYLATED CPG PROBES, FOR WHICH DNA METHYLATION LEVEL WAS HIGHER IN THE GROUPS WITH HIGHEST PAIN GRADES. WE ALSO IDENTIFIED 5,759 HYPOMETHYLATED CPG PROBES FOR WHICH DNA METHYLATION LEVEL WAS LOWER IN THE PAIN GROUPS WITH HIGHER PAIN GRADES. IPA REVEALED THAT PAIN-RELATED DMRS WERE ENRICHED ACROSS MULTIPLE PATHWAYS AND UPSTREAM REGULATORS. THE TOP 10 CANONICAL PATHWAYS WERE LINKED TO CELLULAR SIGNALING PROCESSES RELATED TO IMMUNE RESPONSES (I.E., ANTIGEN PRESENTATION, PD-1, PD-L1 CANCER IMMUNOTHERAPY, B CELL DEVELOPMENT, IL-4 SIGNALING, TH1 AND TH2 ACTIVATION PATHWAY, AND PHAGOSOME MATURATION). MOREOVER, IN TERMS OF UPSTREAM REGULATORS, NDUFAF3 WAS THE MOST SIGNIFICANT (P = 8.6E-04) UPSTREAM REGULATOR. OUR FINDINGS SUPPORT PREVIOUS PRELIMINARY WORK SUGGESTING THE IMPORTANCE OF EPIGENETIC REGULATION OF THE IMMUNE SYSTEM IN KNEE PAIN AND THE NEED FOR FUTURE WORK TO UNDERSTAND THE EPIGENETIC CONTRIBUTIONS TO CHRONIC PAIN.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
13  3477  50 IDENTIFICATION OF ABNORMALLY METHYLATED DIFFERENTIALLY EXPRESSED GENES IN CHRONIC PERIODONTITIS BY INTEGRATED BIOINFORMATICS ANALYSIS. BACKGROUND: DNA METHYLATION PLAYS A VITAL ROLE AS AN EPIGENETIC CHANGE THAT CONTRIBUTES TO CHRONIC PERIODONTITIS. OBJECTIVE: THIS STUDY AIMED TO INTEGRATE TWO METHYLATION DATASETS (GSE173081 AND GSE59962) AND TWO GENE EXPRESSION DATASETS (GSE10334 AND GES16134) TO IDENTIFY ABNORMALLY METHYLATED DIFFERENTIALLY EXPRESSED GENES RELATED TO CHRONIC PERIODONTITIS. METHODS: DIFFERENTIALLY METHYLATED GENES WERE OBTAINED. FUNCTIONAL ENRICHMENT ANALYSIS OF DMGS WAS PERFORMED. THE PROTEIN-PROTEIN INTERACTION (PPI) NETWORK WAS CONSTRUCTED USING STRING AND CYTOSCAPE SOFTWARE. FINALLY, THE HUB GENES WERE SELECTED FROM THE PPI NETWORK BY USING CYTOHUBBA. RESULTS: IN TOTAL, 122 HYPOMETHYLATED AND HIGHLY EXPRESSED GENES WERE ENRICHED IN THE BIOLOGICAL MECHANISMS THAT ARE INVOLVED IN THE DIFFERENTIATION OF EXTRACELLULAR MATRIX ORGANIZATION, EXTRACELLULAR STRUCTURE ORGANIZATION, AND CELL CHEMOTAXIS. THE THREE SELECTED HUB GENES OF THE PPI NETWORK WERE IL1B, KDR, AND MMP9. A TOTAL OF 122 HYPERMETHYLATED AND LOWLY EXPRESSED GENES WERE IDENTIFIED, AND BIOLOGICAL PROCESSES, SUCH AS CORNIFICATION, EPIDERMIS DEVELOPMENT, SKIN DEVELOPMENT, AND KERATINOCYTE DIFFERENTIATION WERE ENRICHED. CDSN DSG1, AND KRT2 WERE IDENTIFIED AS THE TOP 3 HUB GENES OF THE PPI NETWORK. CONCLUSION: BASED ON THE COMPREHENSIVE BIOINFORMATICS ANALYSIS, SIX HUB GENES (IL1B, KDR, MMP9, CDSN DSG1, AND KRT2) WERE ASSOCIATED WITH CHRONIC PERIODONTITIS. OUR FINDINGS PROVIDE NOVEL INSIGHTS INTO THE MECHANISMS UNDERLYING EPIGENETIC CHANGES IN CHRONIC PERIODONTITIS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
14  3609  30 IN UTERO ARSENIC EXPOSURE AND EPIGENOME-WIDE ASSOCIATIONS IN PLACENTA, UMBILICAL ARTERY, AND HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS. EXPOSURE TO ARSENIC EARLY IN LIFE HAS BEEN ASSOCIATED WITH INCREASED RISK OF SEVERAL CHRONIC DISEASES AND IS BELIEVED TO ALTER EPIGENETIC PROGRAMMING IN UTERO. IN THE PRESENT STUDY, WE EVALUATE THE EPIGENOME-WIDE ASSOCIATION OF ARSENIC EXPOSURE IN UTERO AND DNA METHYLATION IN PLACENTA (N = 37), UMBILICAL ARTERY (N = 45) AND HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS (HUVEC) (N = 52) IN A BIRTH COHORT USING THE INFINIUM HUMANMETHYLATION450 BEADCHIP ARRAY. UNADJUSTED AND CELL MIXTURE ADJUSTED ASSOCIATIONS FOR EACH TISSUE WERE EXAMINED ALONG WITH ENRICHMENT ANALYSES RELATIVE TO CPG ISLAND LOCATION AND OMNIBUS PERMUTATION TESTS OF ASSOCIATION AMONG BIOLOGICAL PATHWAYS. ONE CPG IN ARTERY (CG26587014) AND 4 CPGS IN PLACENTA (CG12825509; CG20554753; CG23439277; CG21055948) REACHED A BONFERRONI ADJUSTED LEVEL OF SIGNIFICANCE. SEVERAL CPGS WERE DIFFERENTIALLY METHYLATED IN ARTERY AND PLACENTA WHEN CONTROLLING THE FALSE DISCOVERY RATE (Q-VALUE<0.05), BUT NONE IN HUVEC. ENRICHMENT OF HYPOMETHYLATED CPG ISLANDS WAS OBSERVED FOR ARTERY WHILE HYPERMETHYLATION OF OPEN SEA REGIONS WERE PRESENT IN PLACENTA RELATIVE TO PRENATAL ARSENIC EXPOSURE. THE MELANOGENESIS PATHWAY WAS DIFFERENTIALLY METHYLATED IN ARTERY (MAX F P < 0.001), PLACENTA (MAX F P < 0.001), AND HUVEC (MAX F P = 0.02). SIMILARLY, THE INSULIN-SIGNALING PATHWAY WAS DIFFERENTIALLY METHYLATED IN ARTERY (MAX F P = 0.02), PLACENTA (MAX F P = 0.02), AND HUVEC (MAX F P = 0.02). OUR RESULTS SHOW THAT PRENATAL ARSENIC EXPOSURE CAN ALTER DNA METHYLATION IN ARTERY AND PLACENTA BUT NOT IN HUVEC. FURTHER STUDIES ARE NEEDED TO DETERMINE IF THESE ALTERATIONS IN DNA METHYLATION MEDIATE THE EFFECT OF PRENATAL ARSENIC EXPOSURE AND HEALTH OUTCOMES LATER IN LIFE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
15  3046  42 GENOME-WIDE ANALYSIS OF DNA METHYLATION IDENTIFIES S100A13 AS AN EPIGENETIC BIOMARKER IN INDIVIDUALS WITH CHRONIC (>/= 30 YEARS) TYPE 2 DIABETES WITHOUT DIABETIC RETINOPATHY. BACKGROUND: THIS STUDY AIMED TO DETERMINE THE EPIGENETIC BIOMARKERS OF DIABETIC RETINOPATHY (DR) IN SUBJECTS WITH TYPE 2 DIABETES MELLITUS (T2DM). THIS RETROSPECTIVE STUDY IS BASED ON THE SHANGHAI XINJING COMMUNITY PREVENTION AND TREATMENT ADMINISTRATIVE SYSTEM OF CHRONIC DISEASES. THE SUBJECTS ENROLLED HEREIN WERE T2DM PATIENTS WHO HAD UNDERGONE LONG-TERM FOLLOW-UP EVALUATION IN THE SYSTEM. TWO CONSECUTIVE STUDIES WERE CONDUCTED. IN THE DISCOVERY COHORT, AMONG 19 SUBJECTS WHO HAD DEVELOPED DR WITH A DM DURATION < 3 YEARS AND 21 SUBJECTS WITHOUT DR > 30 YEARS AFTER BEING DIAGNOSED WITH DM, AN INFINIUM HUMAN METHYLATION 850 BEADCHIP WAS USED TO IDENTIFY DIFFERENTIAL METHYLATION REGIONS (DMRS) AND DIFFERENTIAL METHYLATION SITES (DMSS). THE FUNCTION OF THE GENES WAS ASSESSED THROUGH KEGG ENRICHMENT ANALYSIS, GENE ONTOLOGY (GO) ANALYSIS, AND PATHWAY NETWORK ANALYSIS. IN THE REPLICATION COHORT, 87 DR PATIENTS WITH A SHORT DM DURATION AND 89 PATIENTS WITHOUT DR OVER A DM DURATION > 20 YEARS WERE COMPARED TO ASSESS THE ASSOCIATION BETWEEN DMSS AND DR UPON PYROSEQUENCING. RESULTS: A TOTAL OF 34 DMRS WERE IDENTIFIED. GENES CONTAINING DMSS WITH THE TOP 5 HIGHEST BETA VALUE DIFFERENCES BETWEEN DR AND NON-DR PARTICIPANTS WERE LOCATED ON CHROMOSOME 1 AND WERE PRESENT IN THE S100A13 GENE, WHICH WAS ASSOCIATED WITH 71 GO TERMS. TWO S100A13 GENE SITES, I.E., CG02873163 AND CG11343894, DISPLAYED A GOOD CORRELATION WITH DR ON PYROSEQUENCING. CONCLUSIONS: DMSS IN THE S100A13 GENE MAY BE POTENTIAL BIOMARKERS OF DR.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
16  2418  43 EPIGENETIC SIGNATURE OF CHRONIC LOW BACK PAIN IN HUMAN T CELLS. OBJECTIVE: DETERMINE IF CHRONIC LOW BACK PAIN (LBP) IS ASSOCIATED WITH DNA METHYLATION SIGNATURES IN HUMAN T CELLS THAT WILL REVEAL NOVEL MECHANISMS AND POTENTIAL THERAPEUTIC TARGETS AND EXPLORE THE FEASIBILITY OF EPIGENETIC DIAGNOSTIC MARKERS FOR PAIN-RELATED PATHOPHYSIOLOGY. METHODS: GENOME-WIDE DNA METHYLATION ANALYSIS OF 850,000 CPG SITES IN WOMEN AND MEN WITH CHRONIC LBP AND PAIN-FREE CONTROLS WAS PERFORMED. T CELLS WERE ISOLATED (DISCOVERY COHORT, N = 32) AND USED TO IDENTIFY DIFFERENTIALLY METHYLATED CPG SITES, AND GENE ONTOLOGIES AND MOLECULAR PATHWAYS WERE IDENTIFIED. A POLYGENIC DNA METHYLATION SCORE FOR LBP WAS GENERATED IN BOTH WOMEN AND MEN. VALIDATION WAS PERFORMED IN AN INDEPENDENT COHORT (VALIDATION COHORT, N = 63) OF CHRONIC LBP AND HEALTHY CONTROLS. RESULTS: ANALYSIS WITH THE DISCOVERY COHORT REVEALED A TOTAL OF 2,496 AND 419 DIFFERENTIALLY METHYLATED CPGS IN WOMEN AND MEN, RESPECTIVELY. IN WOMEN, MOST OF THESE SITES WERE HYPOMETHYLATED AND ENRICHED IN GENES WITH FUNCTIONS IN THE EXTRACELLULAR MATRIX, IN THE IMMUNE SYSTEM (IE, CYTOKINES), OR IN EPIGENETIC PROCESSES. IN MEN, A UNIQUE CHRONIC LBP DNA METHYLATION SIGNATURE WAS IDENTIFIED CHARACTERIZED BY SIGNIFICANT ENRICHMENT FOR GENES FROM THE MAJOR HISTOCOMPATIBILITY COMPLEX. SEX-SPECIFIC POLYGENIC DNA METHYLATION SCORES WERE GENERATED TO ESTIMATE THE PAIN STATUS OF EACH INDIVIDUAL AND CONFIRMED IN THE VALIDATION COHORT USING PYROSEQUENCING. CONCLUSION: THIS STUDY REVEALS SEX-SPECIFIC DNA METHYLATION SIGNATURES IN HUMAN T CELLS THAT DISCRIMINATES CHRONIC LBP PARTICIPANTS FROM HEALTHY CONTROLS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
17  2406  45 EPIGENETIC RESPONSES TO RHINOVIRUS EXPOSURE IN AIRWAY EPITHELIAL CELLS ARE CORRELATED WITH KEY TRANSCRIPTIONAL PATHWAYS IN CHRONIC RHINOSINUSITIS. BACKGROUND: VIRUSES MAY DRIVE IMMUNE MECHANISMS RESPONSIBLE FOR CHRONIC RHINOSINUSITIS WITH NASAL POLYPOSIS (CRSWNP), BUT LITTLE IS KNOWN ABOUT THE UNDERLYING MOLECULAR MECHANISMS. OBJECTIVES: TO IDENTIFY EPIGENETIC AND TRANSCRIPTIONAL RESPONSES TO A COMMON UPPER RESPIRATORY PATHOGEN, RHINOVIRUS (RV), THAT ARE SPECIFIC TO PATIENTS WITH CRSWNP USING A PRIMARY SINONASAL EPITHELIAL CELL CULTURE MODEL. METHODS: AIRWAY EPITHELIAL CELLS WERE COLLECTED AT SURGERY FROM PATIENTS WITH CRSWNP (CASES) AND FROM CONTROLS WITHOUT SINUS DISEASE, CULTURED, AND THEN EXPOSED TO RV OR VEHICLE FOR 48 H. DIFFERENTIAL GENE EXPRESSION AND DNA METHYLATION (DNAM) BETWEEN CASES AND CONTROLS IN RESPONSE TO RV WERE DETERMINED USING LINEAR MIXED MODELS. WEIGHTED GENE CO-EXPRESSION ANALYSIS (WGCNA) WAS USED TO IDENTIFY (A) CO-REGULATED GENE EXPRESSION AND DNAM SIGNATURES, AND (B) GENES, PATHWAYS, AND REGULATORY MECHANISMS SPECIFIC TO CRSWNP. RESULTS: WE IDENTIFIED 5585 DIFFERENTIAL TRANSCRIPTIONAL AND 261 DNAM RESPONSES (FDR <0.10) TO RV BETWEEN CRSWNP CASES AND CONTROLS. THESE DIFFERENTIAL RESPONSES FORMED THREE CO-EXPRESSION/CO-METHYLATION MODULES THAT WERE RELATED TO CRSWNP AND THREE THAT WERE RELATED TO RV (BONFERRONI CORRECTED P < .01). MOST (95%) OF THE DIFFERENTIALLY METHYLATED CPGS (DMCS) WERE IN MODULES RELATED TO CRSWNP, WHEREAS THE DIFFERENTIALLY EXPRESSED GENES (DEGS) WERE MORE EQUALLY DISTRIBUTED BETWEEN THE CRSWNP- AND RV-RELATED MODULES. GENES IN THE CRSWNP-RELATED MODULES WERE ENRICHED IN KNOWN CRS AND/OR VIRAL RESPONSE IMMUNE PATHWAYS. CONCLUSION: RV ACTIVATES SPECIFIC EPIGENETIC PROGRAMS AND CORRELATED TRANSCRIPTIONAL NETWORKS IN THE SINONASAL EPITHELIUM OF INDIVIDUALS WITH CRSWNP. THESE NOVEL OBSERVATIONS SUGGEST EPIGENETIC SIGNATURES SPECIFIC TO PATIENTS WITH CRSWNP MODULATE RESPONSE TO VIRAL PATHOGENS AT THE MUCOSAL ENVIRONMENTAL INTERFACE. DETERMINING HOW VIRAL RESPONSE PATHWAYS ARE INVOLVED IN EPITHELIAL INFLAMMATION IN CRSWNP COULD LEAD TO THERAPEUTIC TARGETS FOR THIS BURDENSOME AIRWAY DISORDER.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
18  3783  41 INTERFERON-GAMMA PROMOTER HYPOMETHYLATION AND INCREASED EXPRESSION IN CHRONIC PERIODONTITIS. AIM: THE GOAL OF THIS INVESTIGATION WAS TO DETERMINE WHETHER EPIGENETIC MODIFICATIONS IN THE IFNG PROMOTER ARE ASSOCIATED WITH AN INCREASE OF IFNG TRANSCRIPTION IN DIFFERENT STAGES OF PERIODONTAL DISEASES. MATERIALS AND METHODS: DNA WAS EXTRACTED FROM GINGIVAL BIOPSY SAMPLES COLLECTED FROM 47 TOTAL SITES FROM 47 DIFFERENT SUBJECTS: 23 PERIODONTALLY HEALTHY SITES, 12 EXPERIMENTALLY INDUCED GINGIVITIS SITES AND 12 CHRONIC PERIODONTITIS SITES. LEVELS OF DNA METHYLATION WITHIN THE IFNG PROMOTER CONTAINING SIX CPG DINUCLEOTIDES WERE DETERMINED USING PYROSEQUENCING TECHNOLOGY. INTERFERON GAMMA MRNA EXPRESSION WAS ANALYSED BY QUANTITATIVE POLYMERASE CHAIN REACTIONS USING ISOLATED RNA FROM PART OF THE BIOLOGICAL SAMPLES MENTIONED ABOVE. RESULTS: THE METHYLATION LEVEL OF ALL SIX ANALYSED CPG SITES WITHIN THE IFNG PROMOTER REGION IN THE PERIODONTITIS BIOPSIES 52% [INTERQUARTILE RANGE, IQR (43.8%, 63%)] WAS SIGNIFICANTLY LOWER THAN PERIODONTALLY HEALTHY SAMPLES 62% [IQR (51.3%, 74%)], P=0.007 AND GINGIVITIS BIOPSIES 63% [IQR (55%, 74%)], P=0.02. THE TRANSCRIPTIONAL LEVEL OF IFNG IN PERIODONTITIS BIOPSIES WAS 1.96-FOLD AND SIGNIFICANTLY HIGHER THAN TISSUES WITH PERIODONTAL HEALTH (P=0.04). ALTHOUGH THE MRNA LEVEL FROM EXPERIMENTAL GINGIVITIS SAMPLES EXHIBITED AN 8.5-FOLD INCREASE AS COMPARED WITH PERIODONTALLY HEALTHY SAMPLES, NO SIGNIFICANT METHYLATION DIFFERENCE WAS OBSERVED IN EXPERIMENTAL GINGIVITIS SAMPLE. CONCLUSIONS: A HYPOMETHYLATION PROFILE WITHIN IFNG PROMOTER REGION IS RELATED TO AN INCREASE OF IFNG TRANSCRIPTION PRESENT IN THE CHRONIC PERIODONTITIS BIOPSIES, WHILE SUCH AN INCREASE OF IFNG IN EXPERIMENTALLY INDUCED GINGIVITIS SEEMS INDEPENDENT OF PROMOTER METHYLATION ALTERATION.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19  1194  48 CORRELATION OF EPIGENETIC CHANGE AND IDENTIFICATION OF RISK FACTORS FOR ORAL SUBMUCOUS FIBROSIS. BACKGROUND: DNA METHYLATION OF CERTAIN GENES IS AN EPIGENETIC CHANGE THAT IS ESSENTIAL FOR TUMORIGENESIS. ORAL SUBMUCOUS FIBROSIS (OSF) IS A PRECANCEROUS CONDITION OF ORAL MUCOSA WITH INFLAMMATION AND PROGRESSIVE FIBROSIS OF THE LAMINA PROPRIA AND DEEPER CONNECTIVE TISSUE. THE HYPERMETHYLATION OF E-CADHERIN AND CYCLOOXYGENASE 2 (COX-2) IN CHRONIC INFLAMMATION MAY DEMONSTRATE A MILD LESION/MUTATION AT EPIGENETIC LEVELS. THIS STUDY COMPARES THE HYPERMETHYLATION STATUS OF E-CADHERIN AND COX-2 GENES IN PATIENTS WITH ORAL CANCER AND PATIENTS WITH OSF AND ALSO AIMS TO IDENTIFY RISK FACTORS FOR THE DEVELOPMENT OF OSF. METHODS: DNA WAS EXTRACTED FROM BLOOD SAMPLES OF 50 HEALTHY SUBJECTS, 50 PATIENTS WITH OSF AND 60 PATIENTS WITH ORAL CANCER. METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION FOR E-CADHERIN AND COX-2 WAS PERFORMED ON THESE SAMPLES AND THE PRODUCTS WERE ANALYZED ON 2% AGAROSE GEL. SURVEYS ABOUT ORAL HEALTH HABITS AND CLINICAL PERIODONTAL EXAMINATIONS IN PATIENTS WITH OSF AND HEALTHY SUBJECTS WERE ALSO CONDUCTED BY WELL-TRAINED DENTISTS, AND LOGISTIC REGRESSION WAS PERFORMED TO IDENTIFY RISK FACTORS FOR OSF. RESULTS: HYPERMETHYLATION OF E-CADHERIN AND COX-2 WAS OBSERVED IN 36% AND 22% OF ORAL CANCER SAMPLES, RESPECTIVELY. IN PATIENTS WITH OSF, THE RATES WERE 52% AND 30%, AND IN HEALTHY CONTROLS THE RATES WERE 4% AND 6%. HYPERMETHYLATION WAS SHOWN TO BE CORRELATED BETWEEN THE 3 GROUPS WITH STATISTICAL SIGNIFICANCE (P<0.01). METHYLATION OF CPG ISLANDS IN E-CADHERIN AND COX-2 OCCURRED MORE FREQUENTLY IN PATIENTS WITH OSF THAN IN THE CONTROL GROUP, BUT LESS FREQUENTLY THAN IN PATIENTS WITH ORAL CANCER. IN THE LOGISTIC REGRESSION ANALYSIS, SMOKING, BRUSHING MORE THAN TWICE DAILY, PERIODONTAL PROBING DEPTH AND PLAQUE INDEX WERE IDENTIFIED AS 4 MAJOR RISK FACTORS FOR OSF. CONCLUSIONS: THESE DATA CONFIRM THAT E-CADHERIN AND COX-2 EXPRESSIONS ARE RELATED TO OSF. THE EPIGENETIC CHANGES PRESENTED IN PATIENTS WITH CHRONIC INFLAMMATION MIGHT DEMONSTRATE AN IRREVERSIBLE DESTRUCTION IN THE TISSUES OR ORGANS SIMILAR TO THE EFFECTS OF CANCER. CHRONIC OSF WAS SIGNIFICANTLY ASSOCIATED WITH HYPERMETHYLATION, A CANCER RISK FACTOR.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
20  1586  42 DNA METHYLATION PROFILING IDENTIFIES EPIGENETIC DIFFERENCES BETWEEN EARLY VERSUS LATE STAGES OF DIABETIC CHRONIC KIDNEY DISEASE. BACKGROUND: WE INVESTIGATED A CROSS-SECTIONAL EPIGENOME-WIDE ASSOCIATION STUDY OF PATIENTS WITH EARLY AND LATE DIABETES-ASSOCIATED CHRONIC KIDNEY DISEASE (CKD) TO IDENTIFY POSSIBLE EPIGENETIC DIFFERENCES BETWEEN THE TWO GROUPS AS WELL AS CHANGES IN METHYLATION ACROSS ALL STAGES OF DIABETIC CKD. WE ALSO EVALUATED THE POTENTIAL OF USING A PANEL OF IDENTIFIED 5'-C-PHOSPHATE-G-3' (CPG) SITES FROM THIS COHORT TO PREDICT THE PROGRESSION OF DIABETIC CKD. METHODS: THIS CROSS-SECTIONAL STUDY RECRUITED 119 ADULTS. DNA WAS EXTRACTED FROM BLOOD USING THE QIAGEN QIAAMPDNA MINI SPIN KIT. GENOME-WIDE METHYLATION ANALYSIS WAS PERFORMED USING ILLUMINA INFINIUM METHYLATIONEPIC BEADCHIPS (HM850K). INTENSITY DATA FILES WERE PROCESSED AND ANALYSED USING THE MINFI AND MISSMETHYL PACKAGES FOR R. WE EXAMINED THE DEGREE OF METHYLATION OF CPG SITES IN EARLY VERSUS LATE DIABETIC CKD PATIENTS FOR CPG SITES WITH AN UNADJUSTED P-VALUE <0.01 AND AN ABSOLUTE CHANGE IN METHYLATION OF 5% (N = 239 CPG SITES). RESULTS: HIERARCHICAL CLUSTERING OF THE 239 CPG SITES LARGELY SEPARATED THE TWO GROUPS. A HEAT MAP FOR ALL 239 CPG SITES DEMONSTRATED DISTINCT METHYLATION PATTERNS IN THE EARLY VERSUS LATE GROUPS, WITH CPG SITES SHOWING EVIDENCE OF PROGRESSIVE CHANGE. BASED ON OUR DIFFERENTIALLY METHYLATED REGION (DMR) ANALYSIS OF THE 239 CPG SITES, WE HIGHLIGHTED TWO DMRS, NAMELY THE CYSTEINE-RICH SECRETORY PROTEIN 2 (CRISP2) AND PIWI-LIKE RNA-MEDIATED GENE SILENCING 1 (PIWIL1) GENES. THE BEST PREDICTABILITY FOR THE TWO GROUPS INVOLVED A RECEIVER OPERATING CHARACTERISTICS CURVE OF EIGHT CPG SITES ALONE AND ACHIEVED AN AREA UNDER THE CURVE OF 0.976. CONCLUSIONS: WE HAVE IDENTIFIED DISTINCT DNA METHYLATION PATTERNS BETWEEN EARLY AND LATE DIABETIC CKD PATIENTS AS WELL AS DEMONSTRATED NOVEL FINDINGS OF POTENTIAL PROGRESSIVE METHYLATION CHANGES ACROSS ALL STAGES (1-5) OF DIABETIC CKD AT SPECIFIC CPG SITES. WE HAVE ALSO IDENTIFIED ASSOCIATED GENES CRISP2 AND PIWIL1, WHICH MAY HAVE THE POTENTIAL TO ACT AS STAGE-SPECIFIC DIABETES-ASSOCIATED CKD MARKERS, AND SHOWED THAT THE USE OF A PANEL OF EIGHT IDENTIFIED CPG SITES ALONE HELPS TO INCREASE THE PREDICTABILITY FOR THE TWO GROUPS.	2021