1 4184 101 META-PREDICTION OF MTHFR GENE POLYMORPHISM-MUTATIONS, AIR POLLUTION, AND RISKS OF LEUKEMIA AMONG WORLD POPULATIONS. THE MAJOR OBJECTIVE OF THIS STUDY WAS TO EXAMINE THE ASSOCIATION BETWEEN METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) POLYMORPHISMS AND THE RISK OF VARIOUS TYPES OF LEUKEMIAS ACROSS THE LIFESPANS OF CHILDREN AND ADULTS BY USING THE META-PREDICTIVE TECHNIQUES. THE SECONDARY OBJECTIVE WAS TO EXAMINE THE INTERACTIONS AMONG EPIGENETIC RISK FACTORS (INCLUDING AIR POLLUTION), MTHFR POLYMORPHISMS, AND THE RISKS OF DEVELOPING LEUKEMIA. WE COMPLETED A COMPREHENSIVE SEARCH OF 6 DATABASES TO FIND 54 STUDIES (10,033 LEUKEMIA CASES AND 15,835 CONTROLS) FOR MTHFR 677, AND 43 STUDIES (8,868 CASES AND 14,301 CONTROLS) FOR MTHFR 1298, PUBLISHED FROM 1999 TO 2014. THE RESULTS REVEALED THAT, IN EUROPEAN POPULATIONS; CHILDHOOD POPULATIONS; CHILDREN FROM EUROPE, EAST ASIA, AND AMERICA; AND CHILDREN WITH ACUTE LYMPHOCYTIC LEUKEMIA (ALL), MTHFR 677 POLYMORPHISMS (BOTH TT AND CT TYPES TOGETHER AND INDIVIDUALLY) ARE PROTECTIVE, WHILE CC WILDTYPE WAS LEUKEMOGENIC. IN ADDITION, MTHFR 1298 POLYMORPHISMS WERE PROTECTIVE AGAINST ALL AND ACUTE MYELOID LEUKEMIA IN EUROPEAN CHILDREN, AND IN CHRONIC MYELOID LEUKEMIA IN ALL ADULTS WORLDWIDE AND AMERICAN ADULTS. AIR POLLUTION PLAYED A ROLE IN THE INCREASED POLYMORPHISMS OF MTHFR 677 GENOTYPES IN CHILDHOOD LEUKEMIA. 2017 2 5118 35 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 3 5904 23 T677T METHYLENETETRAHYDROFOLATE REDUCTASE SINGLE NUCLEOTIDE POLYMORPHISMS INCREASED PREVALENCE IN A SUBGROUP OF INFERTILE PATIENTS WITH ENDOMETRIOSIS. BACKGROUND: APPROXIMATELY 10% (190 MILLION) OF WOMEN WORLDWIDE ARE AFFECTED BY ENDOMETRIOSIS, ECTOPIC DEPOSITS OF ENDOMETRIAL TISSUE THAT CREATE A MAJOR SOURCE OF PAIN THAT AFFECTS LIFESTYLE AND REPRODUCTIVE FUNCTION. THE PATHOGENESIS OF ENDOMETRIOSIS IS AN ESTROGEN-DEPENDENT INFLAMMATORY PROCESS, INFLUENCED/CATALYZED BY OXIDATIVE STRESS AND CONSEQUENTLY DEFECTIVE METHYLATION, WITH BIOCHEMICAL FEATURES CENTERED AROUND THE FOLATE AND ONE-CARBON CYCLES. WE AIMED TO DETERMINE WHETHER A LINK COULD BE FOUND BETWEEN THE TWO MAJOR METHYLENETETRAHYDROFOLATE REDUCTASE SINGLE NUCLEOTIDE POLYMORPHISMS (MTHFR SNPS), C.677C>T AND C.1298A>C, INVOLVED IN METHYLATION PROCESS/EPIGENETIC MARKING FAILURES, AND ENDOMETRIOSIS. MATERIAL AND METHODS: WE STUDIED A POPULATION OF 158 PATIENTS IN A GROUP OF >1500 REFERRED FOR TREATMENT OF INFERTILITY. ALL THE PATIENTS HAD EXPERIENCED >2 FAILED ASSISTED REPRODUCTIVE TECHNOLOGY CYCLES AND/OR >2 MISCARRIAGES, A CLASSICAL COHORT FOR INVESTIGATION IN OUR GROUP. PATIENTS WITH ENDOMETRIOSIS HAD AT LEAST STAGE 2+ DISEASE CONFIRMED BY LAPAROSCOPY. RESULTS: THE PREVALENCE OF THE HOMOZYGOUS C.677C>T ISOFORM IS DOUBLED IN THE ENDOMETRIOSIS GROUP, 21.5% VERSUS 10.2% IN THE NON-ENDOMETRIOSIS GROUP (P > 0.01). SYMMETRICALLY, THE PERCENTAGE OF PATIENTS IN THE ENDOMETRIOSIS GROUP WITH THE WILD TYPE MTHFR SIGNIFICANTLY DECREASED BY ONE-HALF (8.2%-17.2%) IN THE NON-ENDOMETRIOSIS GROUP (P < 0.001). CONCLUSION: DETERMINATION OF MTHFR C.677C>T SHOULD NOT BE OVERLOOKED IN PATIENTS WITH HARMFUL ENDOMETRIOSIS AFFECTING THEIR FERTILITY. AS FOLATES METABOLISM IS IMPAIRED IN THESE MTHFR SNPS CARRIER PATIENTS, CO-TREATMENT WITH 5-METHYL FOLATE MAY CONSTITUTE A SUCCESSFUL (CO)-TREATMENT MODALITY. 2022 4 1607 30 DNA METHYLATION, COLON CANCER AND MEDITERRANEAN DIET: RESULTS FROM THE EPIC-ITALY COHORT. THE BIOLOGICAL MECHANISMS THROUGH WHICH ADHERENCE TO MEDITERRANEAN DIET (MD) PROTECTS AGAINST COLON CANCER (CC) ARE POORLY UNDERSTOOD. EVIDENCE SUGGESTS THAT CHRONIC INFLAMMATION MAY BE IMPLICATED IN THE PATHWAY. BOTH DIET AND CC ARE RELATED TO EPIGENETIC REGULATION. WE PERFORMED A NESTED CASE-CONTROL STUDY ON 161 PAIRS FROM THE ITALIAN COMPONENT OF THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER AND NUTRITION (EPIC) COHORT, IN WHICH WE LOOKED FOR THE METHYLATION SIGNALS IN DNA EXTRACTED FROM LEUCOCYTES ASSOCIATED WITH BOTH CC AND MD IN 995 CPGS LOCATED IN 48 INFLAMMATION GENES. THE DNA METHYLATION SIGNALS DETECTED IN THIS ANALYSIS WERE VALIDATED IN A SUBGROUP OF 47 CASE-CONTROL PAIRS AND FURTHER REPLICATED (WHERE VALIDATED) IN 95 NEW PAIRS BY MEANS OF PYROSEQUENCING. AMONG THE CPG SITES SELECTED A-PRIORI IN INFLAMMATION-RELATED GENES, SEVEN CPG SITES WERE FOUND TO BE ASSOCIATED WITH CC STATUS AND WITH MD, IN LINE WITH ITS PROTECTIVE EFFECT. ONLY TWO CPG SITES (CG17968347-SERPINE1 AND CG20674490-RUNX3) WERE VALIDATED USING BISULPHITE PYROSEQUENCING AND, AFTER REPLICATION, WE FOUND THAT DNA METHYLATION OF CG20674490-RUNX3 MAY BE A POTENTIAL MOLECULAR MEDIATOR EXPLAINING THE PROTECTIVE EFFECT OF MD ON CC ONSET. THE USE OF A 'MEET-IN-THE-MIDDLE' APPROACH TO IDENTIFY THE OVERLAP BETWEEN EXPOSURE AND PREDICTIVE MARKERS OF DISEASE IS INNOVATIVE IN STUDIES ON THE RELATIONSHIP BETWEEN DIET AND CANCER, IN WHICH EXPOSURE ASSESSMENT IS DIFFICULT AND THE MECHANISMS THROUGH WHICH THE NUTRIENTS EXERT THEIR PROTECTIVE EFFECT IS LARGELY UNKNOWN. 2019 5 6250 31 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 6 4251 27 METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) GENE POLYMORPHISMS RESULTING IN SUBOPTIMAL OOCYTE MATURATION: A DISCUSSION OF FOLATE STATUS, NEURAL TUBE DEFECTS, SCHIZOPHRENIA, AND VASCULOPATHY. SEVERAL CONDITIONS APPARENT AT BIRTH, E.G., NEURAL TUBE DEFECTS (NTDS) AND CARDIAC ANOMALIES, ARE ASSOCIATED WITH POLYMORPHISMS IN FOLATE-RELATED GENES, SUCH AS THE 677C --> T POLYMORPHISM OF THE METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) GENE. SIMILAR ASSOCIATIONS HAVE BEEN ESTABLISHED FOR SEVERAL CONSTITUTIONAL CHRONIC DISEASES IN ADULTHOOD, SUCH AS SCHIZOPHRENIA, CARDIOVASCULAR DISEASES, DEMENTIA, AND EVEN NEOPLASIAS IN DIFFERENT ORGAN SYSTEMS. THIS SPECTRUM OF DEVELOPMENTAL ANOMALIES AND CONSTITUTIONAL DISEASES MAY BE LINKED TO HIGH-RISK CONCEPTIONS RELATED TO PREOVULATORY OVERRIPENESS OVOPATHY (PROO). SOME DEVELOPMENTAL ANOMALIES, SUCH AS NTDS, ARE TO A LARGE EXTENT PREVENTED BY SUPPLEMENTATION OF FOLIC ACID BEFORE CONCEPTION, BUT SUPPLEMENTATION DOES NOT SEEM TO PREVENT CARDIOVASCULAR DISEASE OR COGNITIVE DECLINE. THESE DIVERGING RESULTS CAN BE ELUCIDATED BY INTRODUCTION OF THE PROO CONCEPT, AS MTHFR POLYMORPHISMS AND INHERENT LOW FOLATE LEVELS INDUCE BOTH NON-OPTIMAL MATURATION OF THE OOCYTE AND UNSUCCESSFUL DNA METHYLATION AND DEMETHYLATION, I.E. EPIGENETIC MUTATIONS. THE PROO CONCEPT IS TESTABLE AND PREDICTS IN A RANDOM POPULATION THE FOLLOWING: (1) FEMALE CARRIERS OF SPECIFIC GENETIC MTHFR VARIANTS EXHIBIT MORE OVULATORY DISTURBANCES AND INHERENT SUBFECUNDITY TRAITS, (2) DESCENDENTS FROM A CARRIER MOTHER, WHEN COMPARED WITH THOSE FROM A WILD-TYPE MOTHER, ARE MORE FREQUENTLY CONCEIVED IN PROO HIGH-RISK CONDITIONS AND, THUS, (3) DISADVANTAGED IN LIFE EXPECTANCY. IF SO, SOME MTHFR POLYMORPHISMS REPRESENT A NOVEL, GENETICALLY DETERMINED, PROO HIGH-RISK CONCEPTION CATEGORY COMPARABLE TO THOSE WHICH ARE ENVIRONMENTALLY AND BEHAVIORLY INFLUENCED. THESE HIGH-RISK CONDITIONS MAY CAUSE DEVELOPMENTAL ANOMALIES AND DEFECTIVE EPIGENETIC REPROGRAMMING IN PROGENY. THE INTERACTION BETWEEN GENETIC AND ENVIRONMENTAL FACTORS IS A PLAUSIBLE MECHANISM OF MULTIFACTORIAL INHERITANCE. 2008 7 3442 28 HYPERMETHYLATION IN THE PROMOTER OF THE MTHFR GENE IS ASSOCIATED WITH DIABETIC COMPLICATIONS AND BIOCHEMICAL INDICATORS. BACKGROUND: DNA METHYLATION IS AN EPIGENETIC MECHANISM FOR REGULATING THE TRANSCRIPTION OF MANY GENES AND HAS BEEN LINKED TO THE DEVELOPMENT OF VARIOUS DISEASES. A PROMISING GENE TO INVESTIGATE IS METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR), SINCE THE ENZYME METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) PROMOTES METHYL RADICAL SYNTHESIS IN THE HOMOCYSTEINE CYCLE AND CAN PROVIDE METHYL GROUPS FOR DNA METHYLATION. IN ADDITION, SEVERAL STUDIES HAVE CORRELATED GENE POLYMORPHISMS OF THIS ENZYME WITH A GREATER RISK OF DIABETES, BUT LITTLE IS KNOWN REGARDING THE RELATIONSHIP BETWEEN EPIGENETIC CHANGES IN THIS GENE AND DIABETES AND ITS COMPLICATIONS. THE AIM OF THIS STUDY WAS TO INVESTIGATE THE RELATIONSHIP BETWEEN METHYLATION PROFILE IN THE MTHFR GENE PROMOTER AND BIOCHEMICAL, INFLAMMATORY AND OXIDATIVE STRESS MARKERS IN INDIVIDUALS WITH TYPE 2 DIABETES (T2DM) WHO HAVE BEEN DIAGNOSED FOR 5-10 YEARS WITH OR WITHOUT DIABETIC RETINOPATHY (DR) AND NEPHROPATHY (DN). METHODS: SPECIFIC PCR FOR METHYLATION (MSP) WAS USED TO ANALYZE MTHFR METHYLATION PROFILE IN LEUCOCYTES DNA. BIOCHEMICAL MARKERS (GLYCEMIA, GLYCATED HEMOGLOBIN, TOTAL CHOLESTEROL, LDL, HDL, TRIGLYCERIDES, SERUM CREATININE), INFLAMMATORY MARKERS (C-REACTIVE PROTEIN AND ALPHA-1 ACID GLYCOPROTEIN) AND OXIDATIVE STRESS (TOTAL ANTIOXIDANT AND MALONALDEHYDE) WERE DETERMINED IN PERIPHERIC BLOOD SAMPLES AND MICROALBUMINURIA IN 24 H URINE SAMPLES. THE X(2) AND MANN-WHITNEY STATISTICAL TESTS WERE PERFORMED AND P < 0.05 WERE CONSIDERED SIGNIFICANT. RESULTS: THE HYPERMETHYLATED PROFILE WAS MOST FREQUENTLY OBSERVED IN INDIVIDUALS WITH RETINOPATHY (P < 0.01) AND WAS ASSOCIATED WITH HIGHER TOTAL CHOLESTEROL AND LDL LEVELS (P = 0.0046, 0.0267, RESPECTIVELY). INDIVIDUALS WITH DN AND HYPERMETHYLATED PROFILES HAD HIGHER LEVELS OF ALPHA-1 ACID GLYCOPROTEIN (P = 0.0080) AND TOTAL ANTIOXIDANT CAPACITY (P = 0.0169) COMPARED TO SUBJECTS WITHOUT COMPLICATIONS. CONCLUSIONS: HYPERMETHYLATION IN THE PROMOTER OF THE MTHFR GENE IS ASSOCIATED WITH THE OCCURRENCE OF DR AND WITH BIOCHEMICAL, INFLAMMATORY AND OXIDATIVE STRESS PARAMETERS IN THE CONTEXT OF CHRONIC COMPLICATIONS. 2017 8 1193 28 CORRELATION OF CYP2R1 GENE PROMOTER METHYLATION WITH CIRCULATING VITAMIN D LEVELS AMONG HEALTHY ADULTS. BACKGROUND & OBJECTIVES: DESPITE BEING A TROPICAL COUNTRY, VITAMIN D DEFICIENCY IS HIGHLY PREVALENT IN INDIA WITH STUDIES INDICATING 40-99 PER CENT PREVALENCE. APART FROM CALCIUM AND PHOSPHATE METABOLISM, VITAMIN D IS INVOLVED IN CELL CYCLE REGULATION, CARDIOVASCULAR, HEPATOPROTECTION. THE METABOLISM OF VITAMIN D IS REGULATED BY VITAMIN D TOOL GENES (CYP2R1/CYP27B1/CYP24A1/VDR). THE PROMOTER REGIONS OF SOME OF THESE GENES HAVE CPG ISLANDS, MAKING THEM PRONE TO METHYLATION INDUCED GENE SILENCING, WHICH MAY CAUSE A REDUCTION IN CIRCULATING VITAMIN D LEVELS. EPIGENETIC BASIS OF VITAMIN D DEFICIENCY IS YET TO BE STUDIED IN INDIA, AND HENCE, THIS PILOT STUDY WAS AIMED TO ANALYZE WHETHER METHYLATION LEVELS OF CYP2R1 GENE WERE CORRELATED WITH THE LEVELS OF 25(OH)D IN HEALTHY, ADULT INDIVIDUALS IN INDIAN POPULATION. METHODS: IN THIS CROSS-SECTIONAL STUDY, HEALTHY ADULTS OF 18-45 YR OF AGE WITH NO HISTORY OF MALABSORPTION, THYROIDECTOMY, CHRONIC ILLNESS OR THERAPEUTIC VITAMIN D SUPPLEMENTATION WERE RECRUITED. DNA METHYLATION ANALYSIS WAS CARRIED OUT BY METHYLATION SPECIFIC QUANTITATIVE PCR. SERUM CALCIUM, PHOSPHATE AND VITAMIN D LEVELS WERE ALSO QUANTIFIED. STATISTICAL ANALYSIS WAS DONE BY R 4.0.5 SOFTWARE. RESULTS: A TOTAL OF 61 APPARENTLY HEALTHY ADULTS WERE ANALYZED. THE SERUM VITAMIN D LEVELS DID NOT CORRELATE WITH CYP2R1 METHYLATION LEVELS IN OUR STUDY POPULATION. SIGNIFICANT POSITIVE CORRELATION WAS OBSERVED BETWEEN AGE AND SERUM VITAMIN D LEVELS. SIGNIFICANT ASSOCIATION OF GENDER WAS FOUND WITH CYP2R1 METHYLATION LEVELS. INTERPRETATION & CONCLUSIONS: THIS STUDY FOUND NO SIGNIFICANT CORRELATION BETWEEN LEVELS OF CYP2R1 METHYLATION AND CIRCULATING 25(OH)D DEFICIENCY. FURTHER STUDIES ON THE INDIAN POPULATION HAVING A LARGER SAMPLE SIZE INCLUDING ENTIRE VITAMIN D TOOL GENES, AMONG DIFFERENT ETHNIC GROUPS MAY BE CONDUCTED TO ELUCIDATE MOLECULAR ETIOLOGY OF CIRCULATING 25(OH)D DEFICIENCY. THE HIGH PREVALENCE OF NORMAL SERUM CALCIUM AND PHOSPHATE LEVELS AMONG VITAMIN D DEFICIENT SUBJECTS IN THIS STUDY COUPLED WITH THE STRIKINGLY HIGH PREVALENCE OF THE DEFICIENCY AT THE NATIONAL LEVEL, MAY SUGGEST THE NEED TO REVISE THE CUT-OFF CRITERIA FOR VITAMIN D DEFICIENCY IN THE INDIAN POPULATION. 2023 9 1408 30 DIETARY INTAKE IS ASSOCIATED WITH RESPIRATORY HEALTH OUTCOMES AND DNA METHYLATION IN CHILDREN WITH ASTHMA. BACKGROUND: ASTHMA IS AN INCREASINGLY COMMON CHRONIC DISEASE AMONG CHILDREN, AND DATA POINT TOWARD A COMPLEX MECHANISM INVOLVING GENETIC, ENVIRONMENTAL AND EPIGENETIC FACTORS. EPIGENETIC MODIFICATIONS SUCH AS DNA HYPO- OR HYPER-METHYLATION HAVE BEEN SHOWN TO OCCUR IN RESPONSE TO ENVIRONMENTAL EXPOSURES INCLUDING DIETARY NUTRIENTS. METHODS: WITHIN THE CONTEXT OF THE ASTHMA RANDOMIZED TRIAL OF INDOOR WOOD SMOKE (ARTIS) STUDY, WE INVESTIGATED RELATIONSHIPS BETWEEN DIET, ASTHMA HEALTH MEASURES, AND DNA METHYLATION. ASTHMA HEALTH MEASURES INCLUDED A QUALITY OF LIFE INSTRUMENT, DIURNAL PEAK FLOW VARIABILITY (DPFV) AND FORCED EXPIRATORY VOLUME IN THE FIRST SECOND (FEV(1)). DIETARY INTAKE WAS ASSESSED WITH A FOOD FREQUENCY QUESTIONNAIRE. METHYLATION LEVELS OF LINE-1 REPETITIVE ELEMENT AND TWO PROMOTER CPG SITES FOR INTERFERON GAMMA (IFNGAMMA, -186 AND -54) FROM BUCCAL CELL DNA WERE MEASURED USING PYROSEQUENCING ASSAYS. RESULTS: DATA WERE COLLECTED ON 32 CHILDREN WITH ASTHMA LIVING IN WESTERN MONTANA WHO WERE RECRUITED TO THE ARTIS STUDY. SELENIUM AND SEVERAL METHYL DONOR DIETARY NUTRIENTS WERE POSITIVELY ASSOCIATED WITH THE ASTHMA QUALITY OF LIFE MEASURE. INTAKE OF METHYL DONATING NUTRIENTS INCLUDING FOLATE WAS POSITIVELY ASSOCIATED LINE-1 METHYLATION AND NEGATIVELY ASSOCIATED WITH IFNGAMMA CPG-186. HIGHER LEVELS OF LINE-1 METHYLATION WERE ASSOCIATED WITH GREATER DPFV. CONCLUSION: WE IDENTIFIED SEVERAL NUTRIENTS THAT WERE ASSOCIATED WITH IMPROVED QUALITY OF LIFE MEASURES AMONG CHILDREN WITH ASTHMA. THE IFNGAMMA PROMOTER CPG SITE -186 BUT NOT -54 WAS ASSOCIATED WITH THE INTAKE OF SELECTED DIETARY NUTRIENTS. HOWEVER, IN THIS SMALL POPULATION OF CHILDREN WITH ASTHMA, THE IFNGAMMA PROMOTER CPG SITES WERE NOT ASSOCIATED WITH RESPIRATORY HEALTH MEASURES SO IT REMAINS UNCLEAR THROUGH WHICH EPIGENETIC MECHANISM THESE NUTRIENTS ARE IMPACTING THE QUALITY OF LIFE MEASURE. THESE FINDINGS ADD TO THE EVIDENCE THAT DIETARY NUTRIENTS, PARTICULARLY FOODS CONTAINING METHYL DONORS, MAY BE IMPORTANT FOR EPIGENETIC REGULATION AS IT PERTAINS TO THE CONTROL OF ASTHMA. TRIAL REGISTRATION CLINCIALTRIALS.GOV NCT00807183. REGISTERED 10 DECEMBER 2008. 2017 10 1355 26 DEVELOPMENT AND VALIDATION OF A SIMPLE GENERAL POPULATION LUNG CANCER RISK MODEL INCLUDING AHRR-METHYLATION. INTRODUCTION: SCREENING REDUCES LUNG CANCER MORTALITY OF HIGH-RISK POPULATIONS. CURRENTLY PROPOSED SCREENING ELIGIBILITY CRITERIA ONLY IDENTIFY HALF OF THOSE INDIVIDUALS, WHO LATER DEVELOP LUNG CANCER. THIS STUDY AIMED TO DEVELOP AND VALIDATE A SENSITIVE AND SIMPLE MODEL FOR PREDICTING 10-YEAR LUNG CANCER RISK. METHODS: USING THE 1991-94 EXAMINATION OF THE COPENHAGEN CITY HEART STUDY IN DENMARK, 6,820 FORMER OR CURRENT SMOKERS FROM THE GENERAL POPULATION WERE FOLLOWED FOR LUNG CANCER WITHIN 10 YEARS AFTER EXAMINATION. LOGISTIC REGRESSION OF BASELINE VARIABLES (AGE, SEX, EDUCATION, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, FAMILY HISTORY OF LUNG CANCER, SMOKING STATUS AND CUMULATIVE SMOKING, SECONDHAND SMOKING, OCCUPATIONAL EXPOSURES TO DUST AND FUME, BODY MASS INDEX, LUNG FUNCTION, PLASMA C-REACTIVE PROTEIN, AND AHRR(CG05575921) METHYLATION) IDENTIFIED THE BEST PREDICTIVE MODEL. THE MODEL WAS VALIDATED AMONG 3,740 FORMER OR CURRENT SMOKERS FROM THE 2001-03 EXAMINATION, ALSO FOLLOWED FOR 10 YEARS. A SIMPLE RISK CHART WAS DEVELOPED WITH POISSON REGRESSION. RESULTS: AGE, SEX, EDUCATION, SMOKING STATUS, CUMULATIVE SMOKING, AND AHRR(CG05575921) METHYLATION IDENTIFIED 65 OF 88 INDIVIDUALS WHO DEVELOPED LUNG CANCER IN THE VALIDATION COHORT. THE HIGHEST RISK GROUP, CONSISTING OF LESS EDUCATED MEN AGED >65 WITH CURRENT SMOKING STATUS AND CUMULATIVE SMOKING >20 PACK-YEARS, HAD ABSOLUTE 10-YEAR RISKS VARYING FROM 4% TO 16% BY AHRR(CG05575921) METHYLATION. CONCLUSION: A SIMPLE RISK CHART INCLUDING AGE, SEX, EDUCATION, SMOKING STATUS, CUMULATIVE SMOKING, AND AHRR(CG05575921) METHYLATION, IDENTIFIES INDIVIDUALS WITH 10-YEAR LUNG CANCER RISK FROM BELOW 1% TO 16%. INCLUDING AHRR(CG05575921) METHYLATION IN THE ELIGIBILITY CRITERIA FOR SCREENING IDENTIFIES SMOKERS WHO WOULD BENEFIT THE MOST FROM SCREENING. 2023 11 3568 26 IMPACT OF INFLAMMATION ON EPIGENETIC DNA METHYLATION - A NOVEL RISK FACTOR FOR CARDIOVASCULAR DISEASE? OBJECTIVE: THE LIFESPAN OF DIALYSIS PATIENTS IS AS SHORT AS IN PATIENTS WITH METASTATIC CANCER DISEASE, MAINLY DUE TO CARDIOVASCULAR DISEASE (CVD). DNA METHYLATION IS AN IMPORTANT CELLULAR MECHANISM MODULATING GENE EXPRESSION ASSOCIATED WITH AGEING, INFLAMMATION AND ATHEROSCLEROTIC PROCESSES. DESIGN: DNA METHYLATION WAS ANALYSED IN PERIPHERAL BLOOD LEUCOCYTES FROM THREE DIFFERENT GROUPS OF CHRONIC KIDNEY DISEASE (CKD) POPULATIONS (37 CKD STAGES 3 AND 4 PATIENTS, 98 CKD STAGE 5 PATIENTS AND 20 PREVALENT HAEMODIALYSIS PATIENTS). THIRTY-SIX HEALTHY SUBJECTS SERVED AS CONTROLS. CLINICAL CHARACTERISTICS (DIABETES MELLITUS, NUTRITIONAL STATUS AND PRESENCE OF CLINICAL CVD), INFLAMMATION AND OXIDATIVE STRESS BIOMARKERS, HOMOCYSTEINE AND GLOBAL DNA METHYLATION IN PERIPHERAL BLOOD LEUCOCYTES (DEFINED AS HPAII/MSPI RATIO BY THE LUMINOMETRIC METHYLATION ASSAY METHOD) WERE EVALUATED. CKD STAGE 5 PATIENTS (N=98) STARTING DIALYSIS TREATMENT WERE FOLLOWED FOR A PERIOD OF 36 +/- 2 MONTHS. RESULTS: INFLAMED PATIENTS HAD LOWER RATIOS OF HPAII/MSPI, INDICATING GLOBAL DNA HYPERMETHYLATION. ANALYSIS BY THE COX REGRESSION MODEL DEMONSTRATED THAT DNA HYPERMETHYLATION (HPAII/MSPI RATIO