1 5700 126 SINGLE NUCLEOTIDE POLYMORPHISM IN DNMT3B PROMOTER AND THE RISK FOR IDIOPATHIC THROMBOCYTOPENIC PURPURA IN CHINESE POPULATION. OBJECTIVE: EPIGENETIC CHANGES IN GENE EXPRESSION, INCLUDING DNA METHYLATION AND HISTONE MODIFICATIONS, MIGHT CONTRIBUTE TO AUTOIMMUNITY. DNA METHYLATION IS MEDIATED BY A FAMILY OF DNA METHYLTRANSFERASES. POLYMORPHISMS OF THE DNA METHYLTRANSFERASE 3B (DNMT3B) GENE MAY INFLUENCE DNMT3B ACTIVITY ON DNA METHYLATION, THEREBY MODULATING THE SUSCEPTIBILITY TO SOME DISEASES. THE PURPOSE OF THIS STUDY WAS TO INVESTIGATE THE ASSOCIATION BETWEEN THE SINGLE NUCLEOTIDE POLYMORPHISM (SNP) IN PROMOTER OF THE DNMT3B GENE AND THE RISK FOR DEVELOPMENT OF IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP). METHODS: IN THIS HOSPITAL-BASED CASE-CONTROL STUDY, THE DNMT3B SNP WAS GENOTYPED IN 201 PATIENTS WITH ITP AND 136 HEALTHY CONTROLS BY POLYMERASE CHAIN REACTION-RESTRICTION FRAGMENT LENGTH POLYMORPHISM. RESULTS: THE C/C GENOTYPE WAS NOT DETECTED IN BOTH THE PATIENTS WITH ITP AND THE CONTROLS. IN THE CONTROLS, THE FREQUENCIES OF T/T AND C/T GENOTYPES AND T AND C ALLELES WERE 97.8%, 2.2%, 98.9%, AND 1.1%, RESPECTIVELY. THERE WAS NO SIGNIFICANT DIFFERENCE IN GENOTYPE AND ALLELE DISTRIBUTION BETWEEN THE PATIENTS WITH ITP AND THE CONTROLS (P = 0.745 AND 0.747, RESPECTIVELY). NO SIGNIFICANT DIFFERENCE WAS OBSERVED IN GENOTYPE AND ALLELE DISTRIBUTION BETWEEN THE TWO GROUPS WHEN STRATIFIED BY THE AGE. THE SIMILAR RESULTS WERE SHOWN AMONG THE FOUR GROUPS OF PATIENTS WITH ITP: ACUTE CHILDHOOD, CHRONIC CHILDHOOD, ACUTE ADULT, AND CHRONIC ADULT. CONCLUSION: THIS POLYMORPHISM WAS DISTRIBUTED SIMILARLY BETWEEN THE PATIENTS WITH ITP AND THE CONTROLS. IT DEMONSTRATED THAT IT MAY NOT BE USED AS A STRATIFICATION MARKER TO PREDICT THE SUSCEPTIBILITY TO ITP, AT LEAST IN THE POPULATION OF NORTH CHINA. 2008 2 505 46 ASSOCIATION OF DNA METHYLTRANSFERASE 3B PROMOTOR POLYMORPHISM WITH CHILDHOOD CHRONIC IMMUNE THROMBOCYTOPENIA. BACKGROUND: DNA METHYLATION IS AN EPIGENETIC PROCESS THAT REFERS TO CHROMATIN-BASED MECHANISMS IN THE REGULATION OF GENE EXPRESSION WITHOUT DNA ALTERNATION. IT IS MEDIATED BY DNA METHYLTRANSFERASES (DNMTS). THE DNA METHYLTRANSFERASE 3B (DNMT3B) GENE CONTAINS A C-TO-T SINGLE NUCLEOTIDE POLYMORPHISM (SNP; RS2424913) IN THE PROMOTOR REGION, 149 BASE PAIRS FROM THE TRANSCRIPTION START SITE, WHICH IS REPORTED TO SIGNIFICANTLY INCREASE THE PROMOTOR ACTIVITY. OBJECTIVE: TO INVESTIGATE THE PREVALANCE OF RS2424913 SINGLE NUCLEOTIDE POLYMORPHISM LOCATED IN THE DNMT3B GENE PROMOTOR. METHODS: IN THE PRESENT STUDY, WE INVESTIGATED THE PREVALENCE OF RS2424913 SINGLE NUCLEOTIDE POLYMORPHISM LOCATED IN DNMT3B GENE PROMOTOR BY RESTRICTION FRAGMENT LENGTH POLYMORPHISM (PCR-RFLP) IN EGYPTIAN PEDIATRIC CHRONIC IMMUNE THROMBOCYTOPENIA (ITP) PATIENTS AND CONTROLS. RESULTS: THE HOMOZYGOUS GENOTYPE (TT) WAS SIGNIFICANTLY HIGHER IN OUR PATIENT AND CONFERRED ALMOST 3-FOLD INCREASED RISK OF CHRONIC ITP WHEN COMPARED TO CONTROLS. CONCLUSION: THE PRESENT STUDY SHOWS THAT DNMT3B RS2424913 PROMOTOR POLYMORPHISM REPRESENTS A GENETIC RISK FACTOR THAT MAY PLAY AN IMPORTANT ROLE IN UNDERSTANDING THE PATHOGENESIS OF CHRONIC ITP. 2016 3 3788 37 INTERLEUKIN 1 ALPHA (IL1A) POLYMORPHISMS AND RISK OF ENDOMETRIOSIS IN IRANIAN POPULATION: A CASE-CONTROL STUDY. ENDOMETRIOSIS IS ONE OF THE MOST COMMON GYNECOLOGICAL DISEASES AND A MAJOR CAUSE OF PAIN AND INFERTILITY. IT IS INFLUENCED BY GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. RECENTLY, GENOME-WIDE ASSOCIATION STUDIES HAVE REVEALED A STRONG ASSOCIATION BETWEEN IL1A SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) AND INCREASED RISK OF ENDOMETRIOSIS IN JAPANESE WOMEN. THE AIM OF THE PRESENT STUDY WAS TO EVALUATE THE ASSOCIATION OF THREE IL1A SNPS, RS17561, RS1304037, AND RS2856836 WITH THE RISK OF ENDOMETRIOSIS IN IRANIAN POPULATION. TOTALLY, 105 WOMEN WITH DIAGNOSIS OF ENDOMETRIOSIS AND 102 HEALTHY WOMEN AS CONTROL GROUP WERE INCLUDED. THREE SNPS OF THE IL1A, RS17561 G/T, RS1304037 A/G, AND RS2856836 T/C, WERE GENOTYPED BY PCR AND RFLP. THE RS2856836 TC GENOTYPE WAS SIGNIFICANTLY HIGHER (P = .002; OR = 3.1, 95% CI: 1.5-6.5) IN THE PATIENTS (28.1%) THAN THE CONTROL GROUP (12.7%). THE RS2856836 CC GENOTYPE WAS SIGNIFICANTLY HIGHER (P = .047; OR = 2.3, 95% CI: 1.0-5.3) IN THE PATIENTS (17.5%) THAN THE CONTROL GROUP (10.8%). THE RS2856836 C ALLELE WAS SIGNIFICANTLY HIGHER (P = .001; OR = 2.2, 95% CI: 1.4-3.6) IN THE PATIENTS (31.6%) THAN THE CONTROL GROUP (17.2%). THE IL1A RS2856836 T/C SNP WAS ASSOCIATED WITH SUSCEPTIBILITY TO ENDOMETRIOSIS AND THE RS2856836 C ALLELE MAY INCREASE THE RISK OF ENDOMETRIOSIS IN IRANIAN WOMEN. 2020 4 517 36 ASSOCIATION STUDY OF FOXO3A SINGLE-NUCLEOTIDE POLYMORPHISM AND BRONCHIAL ASTHMA IN EGYPTIAN CHILDREN. ASTHMA IS THE MOST COMMON CHRONIC ILLNESS IN CHILDREN AND IS A LEADING CAUSE OF CHILDHOOD HOSPITALIZATION AND SCHOOL ABSENTEEISM. ASTHMA PRESENTS WITH DIFFERENT PHENOTYPES DEPENDING ON AGE, GENDER, GENETIC BACKGROUND, ENVIRONMENTAL EXPOSURES AND EPIGENETIC FACTORS. FORKHEAD BOX O3 (FOXO3) IS A TRANSCRIPTION FACTOR INVOLVED IN THE PATHOGENESIS OF A NUMBER OF INFLAMMATORY AND RESPIRATORY DISEASES. THE STUDY AIMS TO INVESTIGATE THE ASSOCIATION BETWEEN THE SNP RS13217795 IN FOXO3 GENE AND PEDIATRIC ONSET ASTHMA IN THE EGYPTIAN POPULATION. NINETY ASTHMATICS AND 160 HEALTHY CONTROLS WERE SUBJECTED TO GENOTYPING OF FOXO3 SNP (RS13217795) USING THE PCR-RFLP METHOD. THE PROPORTION OF HOMOZYGOUS (CC) AND HETEROZYGOUS (CT) GENOTYPES WAS LOWER IN THE ASTHMATIC GROUP COMPARED TO THE CONTROL GROUP BUT STATISTICALLY INSIGNIFICANT; P > 0.05. ON THE OTHER HAND THE PROPORTION OF THE MUTANT HOMOZYGOUS (TT) GENOTYPE IN ASTHMATIC GROUP WAS HIGHER; 30 (33.3%) THAN THE CONTROL GROUP; 28(17.5%), THE DIFFERENCE WAS SIGNIFICANT IN RECESSIVE MODEL OF DISEASE PENETRANCE WITH ODDS RATIO OR (95% CI) OF 2.4(1 - 5.49) AND P=0.039. THIS ASSOCIATION WAS MORE PRONOUNCED IN MALE GENDER; OR AND 95% CI OF 5.3 (1.4- 19.3) AND P=0.01. IN CONCLUSIONS, EGYPTIAN CHILDREN CARRYING THE MUTANT (TT) GENOTYPE WERE AT HIGHER RISK TO DEVELOP ASTHMA WITH A HIGHER RISK IN MALE GENDER. 2020 5 3574 44 IMPACT OF METHIONINE SYNTHASE REDUCTASE POLYMORPHISMS IN CHRONIC MYELOID LEUKEMIA PATIENTS. INTRODUCTION: METABOLISM METHIONINE AND OF FOLATE PLAY A VITAL FUNCTION IN CELLULAR METHYLATION REACTIONS, DNA SYNTHESIS AND EPIGENETIC PROCESS.HOWEVER, POLYMORPHISMS OF METHIONINE HAVE RECEIVED MUCH ATTENTION IN RECENT MEDICAL GENETICS RESEARCH. OBJECTIVES: TO ASCERTAIN WHETHER THE COMMON POLYMORPHISMS OF THE MTRR (METHIONINE SYNTHASE REDUCTASE) A66G GENE COULD PLAY A ROLE IN AFFECTING SUSCEPTIBILITY TO CHRONIC MYELOID LEUKEMIA (CML) IN SUDANESE INDIVIDUALS. METHODS: IN A CASE-CONTROLLED STUDY, WE EXTRACTED AND ANALYZED DNA FROM 200 CML PATIENTS AND 100 HEALTHY CONTROL SUBJECTS BY THE PCR-RFLP METHOD. RESULTS: WE FOUND NO SIGNIFICANT DIFFERENCE IN AGE ORGENDER BETWEEN THE PATIENT GROUP AND CONTROLS. THE MTRR A66G GENOTYPES WERE DISTRIBUTED BASED ON THE HARDY-WEINBERG EQUILIBRIUM (P > 0.05). THE VARIATION OF MTRR A66G WAS LESS SIGNIFICANTLY FREQUENT IN CASES WITH CML (68.35%) THAN IN CONTROLS (87%) (OR = 0.146, 95% CI = 0.162-0.662, P < 0.002). ADDITIONALLY, AG AND GG GENOTYPES AND G ALLELE WERE REDUCING THE CML RISK (ODDS RATIO [OR] = 0.365; 95% CI [0.179-0.746]; P = 0.006; OR = 0.292; 95% CI [0.145-0.590]; P = 0.001 AND OR = 0.146; 95% CI [0.162-0.662]; P = 0.002 AND OR = 2.0; 95% CI [1.3853-2.817]; RESPECTIVELY, (P = 0.000)). CONCLUSIONS: OUR DATA DEMONSTRATED THAT HETEROZYGOUS AND HOMOZYGOUS MUTANT GENOTYPES OF MTRR POLYMORPHISMS WERE ASSOCIATED WITH DECREASED RISK OF DEVELOPING CML IN THE SUDANESE POPULATION. 2022 6 2893 30 GAS5 RS2067079 AND MIR-137 RS1625579 FUNCTIONAL SNPS AND RISK OF CHRONIC HEPATITIS B VIRUS INFECTION AMONG EGYPTIAN PATIENTS. HEPATITIS B VIRUS (HBV) INFECTION IS A SIGNIFICANT HEALTH ISSUE WORLDWIDE.. WE ATTEMPTED TO FULFILL THE MOLECULAR MECHANISMS OF EPIGENETIC AND GENETIC FACTORS ASSOCIATED WITH CHRONIC HBV (CHBV). EXPRESSION LEVELS OF THE LNCRNA GROWTH ARREST-SPECIFIC 5 (GAS5) AND MIR-137 AND THEIR CORRESPONDING SNPS, RS2067079 (C/T) AND RS1625579 (G/T) WERE ANALYZED IN 117 CHBV PATIENTS AND 120 CONTROLS TO INVESTIGATE THE PROBABLE ASSOCIATION BETWEEN THESE BIOMARKERS AND CHBV PATHOGENESIS IN THE EGYPTIAN POPULATION. SERUM EXPRESSION LEVELS OF GAS5 AND MIR-137 WERE SIGNIFICANTLY DOWN-REGULATED IN CASES VS CONTROLS. REGARDING GAS5 (RS2067079), THE MUTANT TT GENOTYPE SHOWED AN INCREASED RISK OF CHBV (P < 0.001), WHILE THE DOMINANT CC WAS A PROTECTIVE FACTOR (P = 0.004). REGARDING MIR-137 RS1625579, THE MUTANT GENOTYPE TT WAS REPORTED AS A RISK FACTOR FOR CHBV (P < 0.001) AND THE NORMAL GG GENOTYPE WAS A PROTECTIVE FACTOR, P < 0.001. THE SERUM GAS5 WAS SIGNIFICANTLY HIGHER IN THE MUTANT TT GENOTYPE OF GAS5 SNP AS COMPARED TO THE OTHER GENOTYPES (P = 0.007). CONCERNING MIR-137 RS1625579, THE MUTANT TT GENOTYPE WAS SIGNIFICANTLY ASSOCIATED WITH A LOWER SERUM EXPRESSION LEVEL OF MIR-137 (P = 0.018). WE REVEALED THE DYSREGULATED EXPRESSION LEVELS OF GAS5 AND MIR-137 LINKED TO THEIR FUNCTIONING SNPS WERE ASSOCIATED WITH CHBV RISK AND MIGHT ACT AS POTENTIAL THERAPEUTIC TARGETS. 2021 7 5118 45 POSSIBLE ASSOCIATION BETWEEN GERMLINE METHYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND PSORIASIS RISK IN A TURKISH POPULATION. BACKGROUND: PSORIASIS IS A COMMON CHRONIC INFLAMMATORY SKIN DISEASE CAUSED BY GENETIC AND EPIGENETIC FACTORS. THERE ARE CONFLICTING RESULTS IN THE LITERATURE ABOUT THE ASSOCIATION BETWEEN PSORIASIS AND THE METHYLENETETRAHYDROFOLATE REDUCTASE GENE (MTHFR), RANGING FROM STRONG LINKAGE TO NO ASSOCIATION. AIM: TO INVESTIGATE THE ASSOCIATION BETWEEN THE GERMLINE MTHFR POLYMORPHISMS C677T AND A1298C WITH PSORIASIS RISK IN A TURKISH POPULATION. METHODS: THE STUDY ENROLLED 84 PATIENTS WITH PSORIASIS AND 212 HEALTHY CONTROLS (HCS) WITHOUT ANY HISTORY OF PSORIASIS. DNA WAS EXTRACTED FROM PERIPHERAL BLOOD SAMPLES OF PATIENTS AND HCS, AND REAL-TIME PCR WAS USED FOR GENOTYPING. RESULTS WERE COMPARED BY PEARSON CHI(2) TEST AND MULTIPLE LOGISTIC REGRESSION MODELS. RESULTS: THE FREQUENCY OF BOTH THE MTHFR 677TT AND A1298C (HOMOZYGOUS) GENOTYPES WAS STATISTICALLY SIGNIFICANTLY DIFFERENT FROM HCS. POINT MUTATIONS WERE DETECTED IN ALL PATIENTS WITH EARLY-ONSET PSORIASIS (BEFORE THE AGE OF 20 YEARS). THE T ALLELE OF MTHFR 677 AND THE C ALLELE OF MTHFR 1298 INCREASED PSORIASIS RISK BY 12.4- AND 17.0-FOLD, RESPECTIVELY, IN PATIENTS COMPARED WITH HCS. CONCLUSION: A POSSIBLE ASSOCIATION WAS DETECTED BETWEENGERMLINE MTHFR 677 C>T AND 1298 A>C GENOTYPES AND PSORIASIS RISK IN A TURKISH POPULATION. THESE RESULTS NEED TO BE CONFIRMED IN FURTHER STUDIES WITH LARGER SAMPLE SIZES. 2017 8 4240 25 METHYLATION QUANTITATIVE TRAIT LOCUS ANALYSIS OF CHRONIC POSTSURGICAL PAIN UNCOVERS EPIGENETIC MEDIATORS OF GENETIC RISK. BACKGROUND: OVERLAP OF PATHWAYS ENRICHED BY SINGLE NUCLEOTIDE POLYMORPHISMS AND DNA-METHYLATION UNDERLYING CHRONIC POSTSURGICAL PAIN (CPSP), PROMPTED PILOT STUDY OF CPSP-ASSOCIATED METHYLATION QUANTITATIVE TRAIT LOCI (MEQTL). MATERIALS & METHODS: CHILDREN UNDERGOING SPINE-FUSION WERE RECRUITED PROSPECTIVELY. LOGISTIC-REGRESSION FOR GENOME- AND EPIGENOME-WIDE CPSP ASSOCIATION AND DNA-METHYLATION-SINGLE NUCLEOTIDE POLYMORPHISM ASSOCIATION/MEDIATION ANALYSES TO IDENTIFY MEQTLS WERE FOLLOWED BY FUNCTIONAL GENOMICS ANALYSES. RESULTS: CPSP (N = 20/58) AND NON-CPSP GROUPS DIFFERED IN PAIN-MEASURES. OF 2753 MEQTLS, DNA-METHYLATION AT 127 CYTOSINE-GUANINE DINUCLEOTIDES MEDIATED ASSOCIATION OF 470 MEQTLS WITH CPSP (P < 0.05). AT PARK16 LOCUS, CPSP RISK MEQTLS WERE ASSOCIATED WITH DECREASED DNA-METHYLATION AT RAB7L1 AND INCREASED DNA-METHYLATION AT PM20D1. CORRESPONDING RAB7L1/PM20D1 BLOOD EQTLS (GTEX) AND CYTOSINE-GUANINE DINUCLEOTIDE-LOCI ENRICHMENT FOR HISTONE MARKS, TRANSCRIPTION FACTOR BINDING SITES AND ATAC-SEQ PEAKS SUGGEST ALTERED TRANSCRIPTION FACTOR-BINDING. CONCLUSION: CPSP-ASSOCIATED MEQTLS INDICATE EPIGENETIC MECHANISMS MEDIATE GENETIC RISK. CLINICAL TRIAL REGISTRATION: NCT01839461, NCT01731873 (CLINICALTRIALS.GOV). 2021 9 503 45 ASSOCIATION OF CHEMOKINE GENE VARIANTS WITH END STAGE RENAL DISEASE IN NORTH INDIAN POPULATION. BACKGROUND & AIM: THE PROGRESSION RATE OF CHRONIC KIDNEY DISEASE (CKD) TO ITS END-STAGE RENAL DISEASE (ESRD), AND THE DEVELOPMENT AND SEVERITY OF VARIOUS COMPLICATIONS, ARE INDIRECTLY INFLUENCED BY GENETIC AND EPIGENETIC FACTORS. CHEMOKINES ARE SMALL INDUCIBLE PRO-INFLAMMATORY CYTOKINES, WHICH ARE IMPLICATED IN MANY BIOLOGICAL PROCESSES LIKE MIGRATION OF LEUKOCYTES, ANGIOGENESIS, TUMOR GROWTH AND METASTASIS. WE TESTED ASSOCIATION OF FOUR SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) VIZ. CCL2I/D, CCL2A2518G, CXCL12G801A AND CXCR2(+1208)C/T AMONG INDIVIDUALS WITH ESRD (END STAGE RENAL DISEASE) AND NORMAL HEALTHY CONTROLS FROM NORTH INDIAN POPULATION. MATERIALS AND METHOD: CCL2I/D, CCL2A2518G, CXCL12G801A AND CXCR2(+1208)C/T WERE GENOTYPED IN BLOOD SAMPLES OF HOSPITAL-BASED CASE-CONTROL STUDY COMPRISING OF 200 ESRD CASES AND 200 HEALTHY CONTROLS USING RESTRICTION FRAGMENT LENGTH POLYMORPHISM (RFLP) AND ARMS (AMPLIFICATION REFRACTORY MUTATION SPECIFIC) PCR METHODOLOGY. RESULTS: A SIGNIFICANT ASSOCIATION WAS FOUND IN CXCL12G801A WITH ESRD RISK. IN CASE OF CXCL12G801A POLYMORPHISM HETEROZYGOUS (GA) GENOTYPE SHOWED SIGNIFICANT RISK (P=0.039; OR=1.55) WHEREAS A ALLELE CARRIER (GA+AA) ALSO EXHIBITED RISK WITH ESRD (P=0.045, OR=1.59). IN CXCR2(+1208)C/T POLYMORPHISM, THE HETEROZYGOUS GENOTYPE (CT) SHOWED SIGNIFICANT RISK FOR ESRD (P=0.028; OR=1.65) AND COMBINATION OF CT+TT DEMONSTRATED SIGNIFICANT HIGH RISK FOR ESRD (P=0.036; OR=1.52). IN CASE OF CCL2I/D, THE VARIANT GENOTYPE (D/D) SHOWED REDUCED RISK FOR ESRD PATIENTS. UPON ANALYZING THE GENE-GENE INTERACTION BETWEEN CXCR2 AND CXCL12, THE COMBINATION (CT-GA) SHOWED 2.65 FOLD RISK FOR ESRD (P=0.018). CONCLUSION: OUR RESULTS INDICATED THAT POLYMORPHISM IN CXCL12G801A AND CXCR2(+1208)C/T SHOWED HIGH RISK FOR ESRD IN NORTH INDIAN POPULATION. HOWEVER, CCL2I/D SHOWED REDUCED RISK AND CCL2A2518G EXHIBITED NO ASSOCIATION. STUDY WITH LARGE SAMPLE SIZE AND DIVERSE ETHNICITY IS REQUIRED TO VALIDATE THESE OBSERVATIONS. 2013 10 6250 47 THE METHYLENETETRAHYDROFOLATE REDUCTASE 677C>T GENE POLYMORPHISM IS NOT ASSOCIATED WITH CHRONIC PLAQUE PSORIASIS. BACKGROUND: METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) IS INVOLVED IN THE FORMATION OF METHYL DONORS, WHICH CONTRIBUTE TO DNA METHYLATION. DNA METHYLATION IS AN ESSENTIAL EPIGENETIC FEATURE PLAYING A CRITICAL ROLE IN GENE REGULATION AND CELLULAR DIFFERENTIATION. IN ADDITION, MTHFR ACTIVITY AFFECTS PLASMA HOMOCYSTEINE LEVELS. A FUNCTIONAL POLYMORPHISM IN THE MTHFR GENE (677C>T, RS1801133) LEADING TO REDUCED ENZYME ACTIVITY HAS BEEN ASSOCIATED WITH CHRONIC PLAQUE PSORIASIS IN A CHINESE POPULATION. THIS FINDING, HOWEVER, HAS NOT YET BEEN EITHER CONFIRMED OR REFUTED IN OTHER POPULATIONS. THE PURPOSE OF THE PRESENT STUDY WAS TO INVESTIGATE A HYPOTHESIZED ASSOCIATION BETWEEN THE MTHFR 677C>T POLYMORPHISM AND THE PRESENCE OF CHRONIC PLAQUE PSORIASIS IN A CAUCASIAN POPULATION. METHODS: GENOTYPES FOR THE MTHFR 677C>T POLYMORPHISM WERE DETERMINED IN 310 PATIENTS AND 247 CONTROL SUBJECTS. IN A SUBGROUP OF 33 PATIENTS AND 33 SEX- AND AGE-MATCHED CONTROL SUBJECTS, FASTING PLASMA HOMOCYSTEINE CONCENTRATIONS WERE DETERMINED BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY AND IMMUNOLOGICAL ASSAYS WERE USED FOR THE MEASUREMENT OF FOLATE AND VITAMIN B(12). RESULTS: PREVALENCE OF THE HOMOZYGOUS MTHFR 677TT GENOTYPE DID NOT SIGNIFICANTLY DIFFER BETWEEN PATIENTS AND CONTROLS (15.2% VS 11.7%, P = 0.24). MEAN PLASMA HOMOCYSTEINE CONCENTRATIONS WERE SIGNIFICANTLY HIGHER IN PSORIASIS PATIENTS THAN AMONG CONTROL SUBJECTS (13.5 +/- 5.3 MICROMOL/L VS 11.0 +/- 2.2 MICROMOL/L, P = 0.026). NO SIGNIFICANT DIFFERENCES BETWEEN EITHER MEAN PLASMA FOLATE OR VITAMIN B(12) CONCENTRATIONS WERE OBSERVED BETWEEN BOTH GROUPS. CONCLUSION: OUR DATA SUGGEST THAT THE MTHFR 677C>T GENE POLYMORPHISM IS NOT ASSOCIATED WITH CHRONIC PLAQUE PSORIASIS AMONG CAUCASIANS. 2008 11 3956 48 LONG NON-CODING RNA GENES POLYMORPHISMS H19 (RS2251375) AND MALAT1 (RS3200401) ASSOCIATION WITH RHEUMATOID ARTHRITIS AND THEIR CORRELATION WITH DISEASE ACTIVITY IN A COHORT OF EGYPTIAN PATIENTS: A PILOT STUDY. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC, PROGRESSIVE, INFLAMMATORY, AUTOIMMUNE DISEASE THAT COULD BE DISABLING THROUGHOUT ITS COURSE. IT AFFECTS PEOPLE IN THEIR MOST REPRODUCTIVE YEARS WITH RELATIVELY HIGH MORBIDITY AND MORTALITY. LONG NON-CODING RNAS BECAME ONE OF THE EPIGENETIC MECHANISMS TO PROVE A LINK TO RA PATHOGENESIS AND DEVELOPMENT, INCLUDING H19 AND MALAT1 GENES. THESE TWO GENES' EXPRESSIONS HAD PROVED TO INCREASE IN MULTIPLE DISEASES, ATTRACTING ATTENTION TO THEIR POLYMORPHISMS AND THEIR POSSIBLE RISK ROLE. ASSESS THE ASSOCIATION BETWEEN H19 SNP (RS2251375) AND MALAT1 SNP (RS3200401) AND THE SUSCEPTIBILITY OF RA AND ITS DISEASE ACTIVITY. IN THIS PILOT STUDY, 200 HUNDRED SUBJECTS (100 RA PATIENTS AND 100 HEALTHY CONTROLS) WERE INVESTIGATED FOR A POSSIBLE LINK BETWEEN THE POLYMORPHISMS H19 SNP (RS2251375) AND MALAT1 SNP (3200401) AND RA SUSCEPTIBILITY AND DISEASE ACTIVITY. RA-RELATED INVESTIGATIONS AND CLINICAL ASSESSMENT WERE DONE. REAL-TIME PCR GENOTYPING OF BOTH SNPS WAS DONE USING TAQMAN(R) MGB PROBES. THERE WAS NO ASSOCIATION BETWEEN THE SNPS AND RISK OF DEVELOPING RA. HOWEVER, BOTH SNPS HAD A SIGNIFICANT ASSOCIATION WITH HIGH DISEASE ACTIVITY. H19 SNP (RS2251375) HETEROZYGOUS GENOTYPE CA HAD AN ASSOCIATION WITH ELEVATED LEVELS OF ESR (P = 0.04) AND HIGHER DAS28-ESR SCORE (P = 0.03). MALAT1 (RS3200401) C ALLELE HAD AN ASSOCIATION WITH ELEVATED ESR (P = 0.001), DAS28-ESR (P = 0.03), AND DAS28-CRP (P = 0.007), WHILE CC GENOTYPE HAD AN ASSOCIATION WITH DAS28-CRP (P = 0.015). LINKAGE DISEQUILIBRIUM AND HAPLOTYPING OF THE ALLELES OF BOTH SNPS WERE ANALYZED AS BOTH GENES ARE PRESENT ON CHROMOSOME 11, BUT NO SIGNIFICANT ASSOCIATION WAS FOUND BETWEEN ANY OF THE COMBINATIONS OF THE ALLELES (P > 0.05), DENOTING THAT (RS2251375) AND (RS3200401) ARE NOT IN LINKAGE DISEQUILIBRIUM. THERE IS NO ASSOCIATION BETWEEN H19 SNP (RS2251375) AND MALAT1 SNP (RS3200401) AND THE SUSCEPTIBILITY OF RA. HOWEVER, THERE IS AN ASSOCIATION BETWEEN H19 SNP (RS2251375) GENOTYPE CA AND MALAT1 SNP (RS3200401) GENOTYPE CC WITH RA HIGH DISEASE ACTIVITY. 2023 12 4244 40 METHYLATION STATUS OF COX-2 IN BLOOD LEUKOCYTE DNA AND RISK OF GASTRIC CANCER IN A HIGH-RISK CHINESE POPULATION. BACKGROUND: METHYLATION IS A COMMON EPIGENETIC MODIFICATION WHICH MAY PLAY A CRUCIAL ROLE IN CANCER DEVELOPMENT. TO INVESTIGATE THE ASSOCIATION BETWEEN METHYLATION OF COX-2 IN BLOOD LEUKOCYTE DNA AND RISK OF GASTRIC CANCER (GC), A NESTED CASE-CONTROL STUDY WAS CONDUCTED IN LINQU COUNTY, SHANDONG PROVINCE, A HIGH RISK AREA OF GC IN CHINA. METHODS: ASSOCIATION BETWEEN BLOOD LEUKOCYTE DNA METHYLATION OF COX-2 AND RISK OF GC WAS INVESTIGATED IN 133 GCS AND 285 SUPERFICIAL GASTRITIS (SG)/ CHRONIC ATROPHIC GASTRITIS (CAG). THE TEMPORAL TREND OF COX-2 METHYLATION LEVEL DURING GC DEVELOPMENT WAS FURTHER EXPLORED IN 74 PRE-GC AND 95 POST-GC SAMPLES (INCLUDING 31 CASES WITH BOTH PRE- AND POST-GC SAMPLES). IN ADDITION, THE ASSOCIATION OF DNA METHYLATION AND RISK OF PROGRESSION TO GC WAS EVALUATED IN 74 PRE-GC SAMPLES AND THEIR RELEVANT INTESTINAL METAPLASIA (IM)/DYSPLASIA (DYS) CONTROLS. METHYLATION LEVEL WAS DETERMINED BY QUANTITATIVE METHYLATION-SPECIFIC PCR (QMSP). ODDS RATIOS (ORS) AND 95% CONFIDENCE INTERVALS (CIS) WERE CALCULATED BY UNCONDITIONAL LOGISTIC REGRESSION ANALYSIS. RESULTS: THE MEDIANS OF COX-2 METHYLATION LEVELS WERE 2.3% AND 2.2% IN GC CASES AND CONTROLS, RESPECTIVELY. NO SIGNIFICANT ASSOCIATION WAS FOUND BETWEEN COX-2 METHYLATION AND RISK OF GC (OR, 1.15; 95% CI: 0.70-1.88). HOWEVER, THE TEMPORAL TREND ANALYSIS SHOWED THAT COX-2 METHYLATION LEVELS WERE ELEVATED AT 1-4 YEARS AHEAD OF CLINICAL GC DIAGNOSIS COMPARED WITH THE YEAR OF GC DIAGNOSIS (3.0% VS. 2.2%, P=0.01). FURTHER VALIDATION IN 31 GCS WITH BOTH PRE- AND POST-GC SAMPLES INDICATED THAT COX-2 METHYLATION LEVELS WERE SIGNIFICANTLY DECREASED AT THE YEAR OF GC DIAGNOSIS COMPARED WITH PRE-GC SAMPLES (1.5% VS. 2.5%, P=0.02). NO SIGNIFICANT ASSOCIATION BETWEEN COX-2 METHYLATION AND RISK OF PROGRESSION TO GC WAS FOUND IN SUBJECTS WITH IM (OR, 0.50; 95% CI: 0.18-1.42) OR DYS (OR, 0.70; 95% CI: 0.23-2.18). ADDITIONALLY, WE FOUND THAT ELDER PEOPLE HAD INCREASED RISK OF COX-2 HYPERMETHYLATION (OR, 1.55; 95% CI: 1.02-2.36) AND SUBJECTS WHO EVER INFECTED WITH H. PYLORI HAD DECREASED RISK OF COX-2 HYPERMETHYLATION (OR, 0.54; 95% CI: 0.34-0.88). CONCLUSIONS: COX-2 METHYLATION EXISTS IN BLOOD LEUKOCYTE DNA BUT AT A LOW LEVEL. COX-2 METHYLATION LEVELS IN BLOOD LEUKOCYTE DNA MAY CHANGE DURING GC DEVELOPMENT. 2015 13 514 39 ASSOCIATION OF SHMT1, MAZ, ERG, AND L3MBTL3 GENE POLYMORPHISMS WITH SUSCEPTIBILITY TO MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS) IS THE MOST COMMON INFLAMMATORY AND CHRONIC DISEASE OF THE CENTRAL NERVOUS SYSTEM (CNS). A COMPLEX INTERACTION BETWEEN GENETIC, ENVIRONMENTAL, AND EPIGENETIC FACTORS IS INVOLVED IN THE PATHOGENESIS OF MS. WITH THE ADVANCEMENT OF GWAS, VARIOUS VARIANTS ASSOCIATED WITH MS HAVE BEEN IDENTIFIED. THIS STUDY AIMED TO EVALUATE THE ASSOCIATION OF SINGLE-NUCLEOTIDE POLYMORPHISMS (SNPS) RS4925166 AND RS1979277 IN THE SHMT1, MAZ RS34286592, ERG RS2836425, AND L3MBTL3 RS4364506 WITH MS. IN THIS CASE-CONTROL STUDY, THE ASSOCIATION OF FIVE SNPS IN SHMT1, MAZ, ERG, AND L3MBTL3 GENES WITH RELAPSING-REMITTING MS (RR-MS) WAS INVESTIGATED IN 190 PATIENTS AND 200 HEALTHY INDIVIDUALS. FOUR SNPS INCLUDING SHMT1 RS4925166, SHMT1 RS1979277, MAZ RS34286592, AND L3MBTL3 RS4364506 WERE GENOTYPED USING PCR-RFLP AND GENOTYPING OF ERG RS2836425 WAS PERFORMED BY TETRA-PRIMER ARMS PCR. OUR FINDINGS SHOWED A SIGNIFICANT DIFFERENCE IN THE ALLELIC FREQUENCIES FOR THE FOUR SNPS OF SHMT1 RS4925166, SHMT1 RS1979277, MAZ RS34286592, AND ERG RS2836425, WHILE THERE WERE NO DIFFERENCES IN THE ALLELE AND GENOTYPE FREQUENCIES FOR L3MBTL3 RS4364506. THESE SIGNIFICANT ASSOCIATIONS WERE OBSERVED FOR THE FOLLOWING GENOTYPES: TT AND GG GENOTYPES OF SHMT1 RS4925166 (OR 0.47 AND 1.90, RESPECTIVELY) GENOTYPE GG OF SHMT1 RS1979277 (OR 0.63), GENOTYPE GG OF MAZ RS34286592 (OR 0.61), TC AND CC GENOTYPES OF ERG RS2836425 (OR 1.89 AND 0.50, RESPECTIVELY). OUR STUDY HIGHLIGHTED THAT PEOPLE WHO ARE CARRYING GENOTYPES INCLUDING GG (SHMT1 RS4925166) AND TC (ERG RS2836425) HAVE THE HIGHEST SUSCEPTIBILITY CHANCE FOR MS, RESPECTIVELY. HOWEVER, GENOTYPES TT (SHMT1 RS4925166), CC (ERG RS2836425), GG (MAZ RS34286592), AND GG (SHMT1 RS1979277) HAD THE HIGHEST NEGATIVE ASSOCIATION (PROTECTIVE EFFECT) WITH MS, RESPECTIVELY. L3MBTL3 RS4364506 WAS FOUND NEITHER AS A PREDISPOSING NOR A PROTECTIVE VARIANT. 2019 14 813 43 CHANGES IN POLY(ADP-RIBOSYL)ATION PATTERNS IN WORKERS EXPOSED TO BTX. OCCUPATIONAL EXPOSURE TO (BENZENE, TOLUENE AND XYLENE, BTX IS COMMON IN THE CHINESE WORKPLACE. CHRONIC OCCUPATIONAL EXPOSURE TO BENZENE IS ASSOCIATED WITH AN INCREASED RISK OF HEMATOLOGICAL MALIGNANCIES SUCH AS ACUTE MYELOID LEUKEMIA (AML), BUT THE UNDERLYING MECHANISMS ARE STILL UNCLEAR. THIS STUDY INVESTIGATES CHANGES IN POLY(ADP-RIBOSYL)ATION AND DNA METHYLATION IN SUBJECTS OCCUPATIONALLY EXPOSED TO A BTX. BLOOD DNA SAMPLES AND EXPOSURE DATA WERE OBTAINED FROM SUBJECTS WITH DIFFERENT LEVELS OF EXPOSURE, INCLUDING 132 DECORATORS, 129 PAINTERS, AND 130 UNEXPOSED REFERENTS IN A CONTAINER-MANUFACTURING FACTORY IN SHENZHEN, CHINA. OCCUPATIONAL EXPOSURE ASSESSMENT INCLUDED PERSONAL MONITORING OF AIRBORNE BENZENE, TOLUENE AND XYLENE. HEMATOLOGICAL PARAMETERS WERE MEASURED AND THE CYTOKINESIS-BLOCK MICRONUCLEUS (CBMN) ASSAY WAS USED TO DETECT DNA DAMAGE IN PERIPHERAL LYMPHOCYTES. QUANTITATIVE REAL-TIME PCR WAS USED TO DETECT THE MRNA EXPRESSION OF POLY(ADP-RIBOSE) POLYMERASE 1 (PARP1) AND POLY(ADP-RIBOSE) GLYCOHYDROLASE (PARG), DNA METHYLTRANSFERASES (DNMTS) INCLUDING DNMT1, DNMT3A AND DNMT3B, METHYL-CPG-BINDING DOMAIN PROTEIN 2(MBD2). PARP1 ASSAY WAS USED TO MEASURE PARP ACTIVITY. AIRBORNE LEVELS OF BENZENE, TOLUENE AND XYLENE IN THE TWO EXPOSED GROUPS WERE SIGNIFICANTLY HIGHER THAN THOSE OF CONTROLS (P<0.001). THE TWO EXPOSED GROUPS (DECORATORS, PAINTERS) SHOWED DECREASED PARP1, DNMTS AND MBD2 EXPRESSION RELATIVE TO CONTROLS (P<0.05), AND PARP ACTIVITY WAS ALSO DECREASED (P<0.05). DECREASED PARP1, DNMT1, DNMT3A, DNMT3B AND MBD2 MRNA EXPRESSION WAS CORRELATED WITH INCREASED AIRBORNE BTX (PEARSON'S R: -0.587, -0.314, -0.636, -0.567 AND -0.592 RESPECTIVELY, P<0.001). NO SIGNIFICANT DIFFERENCES IN HEMATOLOGICAL PARAMETERS AND CBMN WERE FOUND AMONG THE THREE GROUPS. TOGETHER, THESE RESULTS SUGGEST THAT DECREASED DNMTS, MBD2 AND PARP1 MIGHT BE INVOLVED IN THE GLOBAL HYPOMETHYLATION ASSOCIATED WITH BTX EXPOSURE, AND THE IMBALANCE OF PARP/PARG MIGHT PARTICIPATE IN THE DOWN-REGULATION OF DNMTS. THIS IS THE FIRST HUMAN STUDY TO LINK ALTERED POLY(ADP-RIBOSYL)ATION PATTERNS, WHICH REPRODUCE THE ABERRANT EPIGENETIC PATTERNS FOUND IN BENZENE-TREATED CELLS, TO CHRONIC OCCUPATIONAL EXPOSURE TO BTX. 2014 15 4245 40 METHYLATION STATUS OF DDIT3 GENE IN CHRONIC MYELOID LEUKEMIA. BACKGROUND: DNA-DAMAGE-INDUCIBLE TRANSCRIPT 3 (DDIT3), A CANDIDATE TUMOR SUPPRESSOR GENE (TSG), HAS BEEN FOUND INVOLVED IN THE REGULATION OF CELLULAR GROWTH AND DIFFERENTIATION. THE EPIGENETIC CHANGES OF TSGS ARE RECENTLY RECOGNIZED AS AN ABNORMAL MECHANISM CONTRIBUTING TO THE DEVELOPMENT OF CHRONIC MYELOID LEUKEMIA (CML). THE AIM OF THIS STUDY WAS TO INVESTIGATE THE METHYLATION STATUS OF DDIT3 GENE IN CML PATIENTS. METHODS: THE METHYLATION STATUS OF DDIT3 PROMOTER WAS DETECTED IN THE BONE MARROW MONONUCLEAR CELLS FROM 53 PATIENTS WITH CML USING METHYLATION-SPECIFIC PCR (MSP). THE EXPRESSION LEVELS OF DDIT3 AND BCR/ABL TRANSCRIPT WERE DETERMINED BY REAL-TIME QUANTITATIVE PCR (RQ-PCR). CLINICAL DATA OF THESE PATIENTS WERE COLLECTED AND ANALYZED. RESULTS: THE ABERRANT METHYLATION OF DDIT3 GENE PROMOTER WAS FOUND IN 35 OF 53 (66%) CML CASES. CORRELATION WAS NOT FOUND BETWEEN DDIT3 PROMOTER HYPERMETHYLATION AND THE AGE, SEX, HEMOGLOBIN CONCENTRATION, PLATELET COUNTS, CHROMOSOMAL ABNORMALITIES, BCR/ABL TRANSCRIPT, AND STAGING OF CML PATIENTS (P > 0.05), BUT FOUND BETWEEN DDIT3 PROMOTER HYPERMETHYLATION AND WBC COUNTS OF CML CASES (R = 0.781, P < 0.001). THE LEVEL OF DDIT3 TRANSCRIPT IN CML PATIENTS WAS SIGNIFICANTLY LOWER THAN THAT IN CONTROLS (MEDIAN 3.28 VS 19.69, P < 0.001), HOWEVER, THERE WAS NO DIFFERENCE IN THE LEVEL OF DDIT3 TRANSCRIPT BETWEEN METHYLATION-POSITIVE CML CASES (0.05-65.32, MEDIAN 2.13) AND METHYLATION- NEGATIVE CML CASES (0.12-126.04, MEDIAN 3.92) (P > 0.05). CONCLUSION: OUR RESULTS DEMONSTRATE THAT ABERRANT METHYLATION OF DDIT3 OCCURS IN CML FREQUENTLY. 2010 16 1991 43 EPIGENETIC ANALYSIS OF THE IFNLAMBDA3 GENE IDENTIFIES A NOVEL MARKER FOR RESPONSE TO THERAPY IN HCV-INFECTED SUBJECTS. CHRONIC HEPATITIS C VIRUS (HCV) INFECTION IS CHARACTERIZED BY HIGH INTERINDIVIDUAL VARIABILITY IN RESPONSE TO PEGYLATED INTERFERON AND RIBAVIRIN. A GENETIC POLYMORPHISM ON CHROMOSOME 19 (RS12979860) UPSTREAM OF INTERFERON-LAMBDA3 (IFNLAMBDA3) IS ASSOCIATED WITH A TWOFOLD CHANGE IN SUSTAINED VIROLOGIC RESPONSE RATE AFTER 48 WEEKS OF TREATMENT WITH PEGYLATED INTERFERON/RIBAVIRIN IN HCV GENOTYPE 1 (GT1) TREATMENT-NAIVE PATIENTS. WE CONDUCTED EPIGENETIC ANALYSIS ON THE IFNLAMBDA3 PROMOTER TO INVESTIGATE WHETHER DNA METHYLATION IS ASSOCIATED WITH RESPONSE TO HCV THERAPY. DNA SAMPLES FROM HCV GT1-INFECTED SUBJECTS RECEIVING AN INTERFERON-FREE PARITAPREVIR-CONTAINING COMBINATION REGIMEN (N=540) AND FROM HCV-UNINFECTED, HEALTHY CONTROLS (N=124) WERE ANALYSED FOR IFNLAMBDA3 METHYLATION LEVELS. METHYLATION WAS STRONGLY ASSOCIATED WITH RS12979860 ALLELE STATUS WHETHER ADJUSTING FOR HCV STATUS (R=65.0%, 95% CI: [60.2%, 69.5%]), OR NOT (R=64.4%), BOTH WITH P<2.2X10(-16) . IN HCV GT1-INFECTED SUBJECTS, C/C GENOTYPES HAD SIGNIFICANTLY LOWER METHYLATION LEVELS RELATIVE TO C/T OR T/T GENOTYPES (P<1X10(-14) ), WITH EACH T ALLELE RESULTING IN A NINE-UNIT INCREASE IN MEAN METHYLATION LEVEL. METHYLATION LEVELS DID NOT CORRELATE WITH RESPONSE IN SUBJECTS TREATED FOR 12 OR 24 WEEKS. HOWEVER, NON-C/C SUBJECTS WITH HIGHER METHYLATION LEVELS WERE MORE LIKELY TO RELAPSE WHEN TREATMENT DURATION WAS 8 WEEKS. THIS ANALYSIS SUGGESTS THAT METHYLATION STATUS OF THE IFNLAMBDA3 PROMOTER REGION MAY BE A USEFUL PARAMETER THAT IDENTIFIES PATIENTS MORE LIKELY TO RELAPSE FOLLOWING HCV THERAPY; HOWEVER, CONTINUING THERAPY FOR A SUFFICIENT DURATION CAN OVERCOME THIS DIFFERENCE. THESE FINDINGS MAY PROVIDE MECHANISTIC INSIGHT INTO THE ROLE OF IFNLAMBDA3 GENETIC VARIANTS IN HCV TREATMENT RESPONSE. 2017 17 3528 42 IL36G GENETIC VARIANT IS INDEPENDENTLY ASSOCIATED WITH SUSCEPTIBILITY, SEVERITY AND JOINT INVOLVEMENT IN PSORIASIS. PSORIASIS (PSO) IS A CHRONIC, IMMUNE-MEDIATED, INFLAMMATORY AND POLYGENIC DERMATOSIS ASSOCIATED WITH BOTH PHYSICAL AND PSYCHOLOGICAL BURDEN THAT CAN BE TRIGGERED BY INJURY, TRAUMA, INFECTIONS AND MEDICATIONS. THE ETIOLOGY OF PSO IS NOT FULLY ELUCIDATED BUT GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS ARE ALL LIKELY TO PLAY A ROLE. A CASE-CONTROL STUDY WAS CARRIED OUT TO EVALUATE THE FREQUENCY OF THE IL36G C>T (RS13392494) AND THE IL36G A>G (RS7584409) VARIANTS AND THEIR ASSOCIATION WITH SUSCEPTIBILITY, JOINT INVOLVEMENT AND SEVERITY OF PSO. THE STUDY INCLUDED 154 PATIENTS WITH PSO AND 154 CONTROLS FROM BRAZILIAN POPULATION. THE SEVERITY OF PSO WAS ASSESSED BY THE PSORIASIS AREA AND SEVERITY INDEX (PASI). THE IL36G (RS13392494 AND RS7584409) VARIANTS WERE GENOTYPED BY ALLELIC DISCRIMINATION ASSAY USING THE REAL-TIME POLYMERASE CHAIN REACTION. THE ASSOCIATION BETWEEN THE IL36G GENETIC VARIANTS AND THE STUDY VARIABLES WAS ANALYZED IN ALLELIC, DOMINANT, CODOMINANT, OVERDOMINANT, RECESSIVE, AND HAPLOTYPE MODELS. THE MAIN RESULTS WERE THAT PSO PATIENTS WERE OLDER (P < 0.001) AND HAD HIGHER BODY MASS INDEX (P < 0.001) THAN CONTROLS; 95.8% OF THE PATIENTS HAD PLAQUE PSO, 16.1% HAD PSORIATIC ARTHRITIS (PSA), AND 27.9% HAD PASI > 10. THE IL36G RS1339294 VARIANT SHOWED NO ASSOCIATION WITH PSO IN ALL GENETIC MODELS WHILE THE IL36G RS7584409 VARIANT SHOWED A PROTECTIVE EFFECT IN PSO. HOWEVER, THE G ALLELE OF THE IL36G RS7584409 IN THE DOMINANT MODEL WAS POSITIVELY ASSOCIATED WITH PASI > 10 (P = 0.031). MOREOVER, PATIENTS WITH THE GG GENOTYPE OF THE IL36G RS7584409 VARIANT HAD ABOUT 5.0 TIMES MORE CHANCE OF PSA THAN THOSE WITH THE AA GENOTYPE (P = 0.014). REGARDING THE HAPLOTYPES, THE C/A IN A RECESSIVE MODEL (CACA VERSUS C/G AND T/A CARRIERS) WAS ASSOCIATED WITH PSO (P = 0.035) WHILE THE C/G HAPLOTYPE IN A DOMINANT MODEL (C/A CARRIERS VERSUS C/G AND T/A CARRIERS) SHOWED A PROTECTIVE EFFECT FOR PSO (P = 0.041). IN CONCLUSION, THE G ALLELE OF THE IL36G RS7584409 VARIANT WAS ASSOCIATED WITH PROTECTION TO PSO; HOWEVER, IN PATIENTS WITH PSO, THIS SAME ALLELE WAS ASSOCIATED WITH MODERATE TO SEVERE DISEASE AND PSA. THESE RESULTS SUGGEST THAT THE IL36G RS7584409 VARIANT MAY BE USED AS A POSSIBLE GENETIC BIOMARKER TO PREDICT SEVERITY AND JOINT INVOLVEMENT OF PSO. 2023 18 3083 37 GENOME-WIDE SCREEN OF DNA METHYLATION CHANGES INDUCED BY LOW DOSE X-RAY RADIATION IN MICE. EPIGENETIC MECHANISMS PLAY A KEY ROLE IN NON-TARGETED EFFECTS OF RADIATION. THE PURPOSE OF THIS STUDY WAS TO INVESTIGATE GLOBAL HYPOMETHYLATION AND PROMOTER HYPERMETHYLATION OF PARTICULAR GENES INDUCED BY LOW DOSE RADIATION (LDR). THIRTY MALE BALB/C MICE WERE DIVIDED INTO 3 GROUPS: CONTROL, ACUTELY EXPOSED (0.5 GY X-RAYS), AND CHRONIC EXPOSURE FOR 10 DAYS (0.05GY/DX10D). HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) AND MEDIP-QUANTITATIVE POLYMERASE CHAIN REACTION (QPCR) WERE USED TO STUDY METHYLATION PROFILES. DNMT1 AND MBD2 EXPRESSION WAS DETERMINED BY QPCR AND WESTERN BLOT ASSAYS. METHYLATION AND EXPRESSION OF RAD23B AND DDIT3 WERE DETERMINED BY BISULFATE SEQUENCING PRIMERS (BSP) AND QPCR, RESPECTIVELY. THE RESULTS SHOW THAT LDR INDUCED GENOMIC HYPOMETHYLATION IN BLOOD 2 H POSTIRRADITAION, BUT WAS NOT RETAINED AT 1-MONTH. DNMT1 AND MBD2 WERE DOWNREGULATED IN A TISSUE-SPECIFIC MANNER BUT DID NOT PERSIST. SPECIFIC HYPERMETHYLATION WAS OBSERVED FOR 811 REGIONS IN THE GROUP RECEIVING CHRONIC EXPOSURE, WHICH COVERED ALMOST ALL KEY BIOLOGICAL PROCESSES AS INDICATED BY GO AND KEGG PATHWAY ANALYSIS. EIGHT HYPERMETHYLATED GENES (RAD23B, TDG, CCND1, DDIT3, LLGL1, RASL11A, TBX2, SCL6A15) WERE VERIFIED BY MEDIP-QPCR. AMONG THEM, RAD23B AND DDIT3 GENE DISPLAYED TISSUE-SPECIFIC METHYLATION AND DOWNREGULATION, WHICH PERSISTED FOR 1-MONTH POSTIRRADIATION. THUS, LDR INDUCED GLOBAL HYPOMETHYLATION AND TISSUE-SPECIFIC PROMOTER HYPERMETHYLATION OF PARTICULAR GENES. PROMOTER HYPERMETHYLATION, RATHER THAN GLOBAL HYPOMETHYLATION, WAS RELATIVELY STABLE. DYSREGULATION OF METHYLATION MIGHT BE CORRELATED WITH DOWN-REGULATION OF DNMT1 AND MBD2, BUT MUCH BETTER UNDERSTANDING THE MOLECULAR MECHANISMS INVOLVED IN THIS PROCESS WILL REQUIRE FURTHER STUDY. 2014 19 2870 51 FUNCTIONAL GENE POLYMORPHISMS AND EXPRESSION ALTERATION OF SELECTED MICRORNAS AND THE RISK OF VARIOUS GASTRIC LESIONS IN HELICOBACTER PYLORI-RELATED GASTRIC DISEASES. BACKGROUND: HELICOBACTER PYLORI (HP) PERSISTENT INFECTION IS AN IMPORTANT PATHOGENIC FACTOR FOR A SERIES OF CHRONIC GASTRIC DISEASES FROM CHRONIC GASTRITIS TO GASTRIC CANCER. GENETIC AND EPIGENETIC ABNORMALITIES OF MICRORNAS MAY PLAY A VITAL ROLE IN THE PATHOLOGICAL EVOLUTION OF GASTRIC MUCOSA IN HELICOBACTER PYLORI-RELATED GASTRIC DISEASES (HPGD). THIS STUDY AIMED TO INVESTIGATE THE RELATIONSHIP BETWEEN MIR-146A, MIR-196A2, MIR-149, MIR-499 AND MIR-27A GENE SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) AND THEIR EXPRESSIONS WITH PATHOLOGICAL CHANGES IN GASTRIC MUCOSA, AND TO FURTHER ANALYZE THE INTERACTIONS BETWEEN SNPS AND HP. METHODS: SUBJECTS IN THIS STUDY INCLUDED PATIENTS DIAGNOSED WITH HPGD AND HEALTHY CONTROLS. MIR-146A RS2910164, MIR-196A2 RS11614913, MIR-149 RS2292832, MIR-499 RS3746444 AND MIR-27A RS895819 WERE GENOTYPED BY DIRECT SEQUENCING. FLUORESCENCE QUANTITATIVE PCR WAS USED TO DETECT MICRORNA EXPRESSIONS. GENE-GENE AND GENE-ENVIRONMENT INTERACTIONS WERE EVALUATED BY MULTIFACTOR DIMENSIONALITY REDUCTION (MDR) METHOD. RESULTS: WE FOUND THAT FREQUENCY DISTRIBUTION OF MIR-196A2 RS11614913 CT GENOTYPE IN GASTRIC PRECANCEROUS LESION (GPL) GROUP AND GASTRIC CANCER (GC) GROUP WAS SIGNIFICANTLY HIGHER THAN NORMAL CONTROL (NOR) GROUP [ADJUSTED OR = 6.16, 95%CI (1.46-26.03); ADJUSTED OR = 11.83, 95%CI (1.65-84.72), RESPECTIVELY]. CT GENOTYPE AND C ALLELE OF MIR-27A RS895819 WERE ASSOCIATED WITH INCREASED RISK OF GC [ADJUSTED OR = 10.14, 95%CI (2.25-45.77); ADJUSTED OR = 3.71, 95%CI(1.46-9.44), RESPECTIVELY]. THE MDR ANALYSIS RESULTS SHOWED THAT THE INTERACTION BETWEEN MIR-196A2 RS11614913 AND HP WAS ASSOCIATED WITH THE RISK OF GPL (P = 0.004). MEANWHILE, THE EXPRESSION LEVEL OF MIR-196A2 IN GC GROUP WAS SIGNIFICANTLY HIGHER THAN NOR, CHRONIC INFLAMMATION (CI) AND EARLY PRECANCEROUS LESION (EPL) GROUPS AMONG HP-POSITIVE SUBJECTS. AND EXPRESSIONS OF MIR-499 AND MIR-27A IN GC GROUP WERE BOTH HIGHER THAN EPL GROUP. ALSO, MIR-27A EXPRESSION IN GC GROUP WAS HIGHER THAN CI AND GASTRIC ATROPHY (GA) GROUPS. CONCLUSION: MIR-196A2 RS11614913 AND MIR-27A RS895819 MAY AFFECT THE GENETIC SUSCEPTIBILITY TO GPL OR GC. MIR-196A2 RS11614913 AND HP HAVE A SYNERGISTIC EFFECT IN THE OCCURRENCE AND DEVELOPMENT OF GPL. THE UP-REGULATION OF MIR-499, MIR-196A2 AND MIR-27A EXPRESSION CAUSED BY HP INFECTION MAY BE AN IMPORTANT MECHANISM OF GASTRIC CARCINOGENESIS. 2022 20 6248 33 THE METHYLATION STATUS OF THE DDX43 PROMOTER IN CHINESE PATIENTS WITH CHRONIC MYELOID LEUKEMIA. ABERRANT DNA METHYLATION IS A COMMON EPIGENETIC ALTERATION AND AN IMPORTANT FEATURE IN HUMAN CANCERS. THE DEAD BOX POLYPEPTIDE 43 (DDX43) HAS BEEN FOUND TO BE OVEREXPRESSED IN VARIOUS SOLID TUMORS AND SOME HEMATOLOGIC MALIGNANCIES. IN THE PRESENT STUDY, WE INVESTIGATED THE METHYLATION STATUS OF THE DDX43 PROMOTER IN 87 CHINESE PATIENTS WITH CHRONIC MYELOID LEUKEMIA (CML) USING REAL-TIME QUANTITATIVE METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION AND EXAMINED THE DDX43 TRANSCRIPT IN 35 PATIENTS USING REAL-TIME QUANTITATIVE POLYMERASE CHAIN REACTION. DDX43 PROMOTER HYPOMETHYLATION WAS OBSERVED IN 22 (25.3%) CML PATIENTS. NO SIGNIFICANT CORRELATION WAS FOUND BETWEEN THE HYPOMETHYLATION OF THE DDX43 PROMOTER WITH THE AGE, SEX, WHITE BLOOD CELL COUNTS, HEMOGLOBIN CONCENTRATION, PLATELET COUNTS, AND CHROMOSOMAL ABNORMALITIES OF CML PATIENTS (P>0.05). THE FREQUENCY OF DDX43 HYPOMETHYLATION IN PATIENTS IN THE CHRONIC PHASE, IN THE ACCELERATED PHASE, AND IN BLAST CRISIS WAS 23.4% (15/64), 25.0% (2/8), AND 33.3% (5/15), RESPECTIVELY (P>0.05). THERE WAS A SIGNIFICANT CORRELATION BETWEEN DDX43 HYPOMETHYLATION AND DDX43 TRANSCRIPT (R=0.469, P=0.004). OUR DATA SUGGEST THAT HYPOMETHYLATION OF THE DDX43 PROMOTER MAY BE AN EARLY AND FREQUENT MOLECULAR EVENT IN THE DEVELOPMENT OF CML IN CHINESE PATIENTS. 2013