1 2044 120 EPIGENETIC CLOCK ANALYSIS OF BLOOD SAMPLES IN DRUG-NAIVE FIRST-EPISODE SCHIZOPHRENIA PATIENTS. BACKGROUND: SCHIZOPHRENIA (SCZ) IS A SEVERE AND CHRONIC PSYCHIATRIC DISORDER WITH PREMATURE AGE-RELATED PHYSIOLOGICAL CHANGES. HOWEVER, NUMEROUS PREVIOUS STUDIES EXAMINED THE EPIGENETIC AGE ACCELERATION IN SCZ PATIENTS AND YIELDED INCONCLUSIVE RESULTS. IN THIS STUDY, WE PROPOSE TO EXPLORE THE EPIGENETIC AGE ACCELERATION IN DRUG-NAIVE FIRST-EPISODE SCZ (FSCZ) PATIENTS AND INVESTIGATE WHETHER EPIGENETIC AGE ACCELERATION IS ASSOCIATED WITH ANTIPSYCHOTIC TREATMENT, PSYCHOTIC SYMPTOMS, COGNITION, AND SUBCORTICAL VOLUMES. METHODS: WE ASSESSED THE EPIGENETIC AGE IN 38 DRUG-NAIVE FSCZ PATIENTS AND 38 HEALTHY CONTROLS BY USING THREE INDEPENDENT CLOCKS, INCLUDING HORVATH, HANNUM AND LEVINE ALGORITHMS. THE EPIGENETIC AGE MEASUREMENTS IN SCZ PATIENTS WERE REPEATED AFTER RECEIVING 8 WEEKS RISPERIDONE MONOTHERAPY. RESULTS: OUR FINDINGS SHOWED SIGNIFICANTLY POSITIVE CORRELATIONS BETWEEN EPIGENETIC AGES ASSESSED BY THREE CLOCKS AND CHRONOLOGICAL AGE IN BOTH FSCZ PATIENTS AND HEALTHY CONTROLS. COMPARED WITH HEALTHY CONTROLS, DRUG-NAIVE FSCZ PATIENTS HAVE A SIGNIFICANT EPIGENETIC AGE DECELERATION IN HORVATH CLOCK (P = 0.01), BUT NOT IN HANNUM CLOCK (P = 0.07) AND LEVINE CLOCK (P = 0.43). THE EPIGENETIC AGES OF HANNUM CLOCK (P = 0.002) AND LEVINE CLOCK (P = 0.01) WERE SIGNIFICANTLY ACCELERATED IN SCZ PATIENTS AFTER 8-WEEK RISPERIDONE TREATMENT. HOWEVER, NO SIGNIFICANT ASSOCIATIONS BETWEEN EPIGENETIC AGE ACCELERATION AND PSYCHOTIC SYMPTOMS, COGNITIVE FUNCTION, AS WELL AS SUBCORTICAL VOLUMES WERE OBSERVED IN FSCZ PATIENTS. CONCLUSION: THESE RESULTS DEMONSTRATE THAT DISTINCT EPIGENETIC CLOCKS ARE SENSITIVE TO DIFFERENT ASPECTS OF AGING PROCESS. FURTHER INVESTIGATIONS WITH COMPREHENSIVE EPIGENETIC CLOCK ANALYSES AND LARGE SAMPLES ARE REQUIRED TO CONFIRM OUR FINDINGS. 2023 2 5267 35 PROMOTER ACTIVITY-BASED CASE-CONTROL ASSOCIATION STUDY ON SLC6A4 HIGHLIGHTING HYPERMETHYLATION AND ALTERED AMYGDALA VOLUME IN MALE PATIENTS WITH SCHIZOPHRENIA. ASSOCIATIONS BETWEEN ALTERED DNA METHYLATION OF THE SEROTONIN TRANSPORTER (5-HTT)-ENCODING GENE SLC6A4 AND EARLY LIFE ADVERSITY, MOOD AND ANXIETY DISORDERS, AND AMYGDALA REACTIVITY HAVE BEEN REPORTED. HOWEVER, FEW STUDIES HAVE EXAMINED EPIGENETIC ALTERATIONS OF SLC6A4 IN SCHIZOPHRENIA (SZ). WE EXAMINED CPG SITES OF SLC6A4, WHOSE DNA METHYLATION LEVELS HAVE BEEN REPORTED TO BE ALTERED IN BIPOLAR DISORDER, USING 3 INDEPENDENT COHORTS OF PATIENTS WITH SZ AND AGE-MATCHED CONTROLS. WE FOUND SIGNIFICANT HYPERMETHYLATION OF A CPG SITE IN SLC6A4 IN MALE PATIENTS WITH SZ IN ALL 3 COHORTS. WE SHOWED THAT CHRONIC ADMINISTRATION OF RISPERIDONE DID NOT AFFECT THE DNA METHYLATION STATUS AT THIS CPG SITE USING COMMON MARMOSETS, AND THAT IN VITRO DNA METHYLATION AT THIS CPG SITE DIMINISHED THE PROMOTER ACTIVITY OF SLC6A4. WE THEN GENOTYPED THE 5-HTT-LINKED POLYMORPHIC REGION (5-HTTLPR) AND INVESTIGATED THE RELATIONSHIP AMONG 5-HTTLPR, DNA METHYLATION, AND AMYGDALA VOLUME USING BRAIN IMAGING DATA. WE FOUND THAT PATIENTS HARBORING LOW-ACTIVITY 5-HTTLPR ALLELES SHOWED HYPERMETHYLATION AND THEY SHOWED A NEGATIVE CORRELATION BETWEEN DNA METHYLATION LEVELS AND LEFT AMYGDALA VOLUMES. THESE RESULTS SUGGEST THAT HYPERMETHYLATION OF THE CPG SITE IN SLC6A4 IS INVOLVED IN THE PATHOPHYSIOLOGY OF SZ, ESPECIALLY IN MALE PATIENTS HARBORING LOW-ACTIVITY 5-HTTLPR ALLELES. 2020 3 1554 38 DNA METHYLATION LEVELS OF RELN PROMOTER REGION IN ULTRA-HIGH RISK, FIRST EPISODE AND CHRONIC SCHIZOPHRENIA COHORTS OF SCHIZOPHRENIA. THE ESSENTIAL ROLE OF THE REELIN GENE (RELN) DURING BRAIN DEVELOPMENT MAKES IT A PROMINENT CANDIDATE IN HUMAN EPIGENETIC STUDIES OF SCHIZOPHRENIA. PREVIOUS LITERATURE HAS REPORTED DIFFERING LEVELS OF DNA METHYLATION (DNAM) IN PATIENTS WITH PSYCHOSIS. THEREFORE, THIS STUDY AIMED TO (1) EXAMINE AND COMPARE RELN DNAM LEVELS IN SUBJECTS AT DIFFERENT STAGES OF PSYCHOSIS CROSS-SECTIONALLY, (2) ANALYSE THE EFFECT OF ANTIPSYCHOTICS (AP) ON DNAM, AND (3) EVALUATE THE EFFECTIVENESS AND APPLICABILITY OF RELN PROMOTER DNAM AS A POSSIBLE BIOLOGICAL-BASED MARKER FOR SYMPTOM SEVERITY IN PSYCHOSIS.. THE STUDY COHORT CONSISTED OF 56 HEALTHY CONTROLS, 87 ULTRA-HIGH RISK (UHR) INDIVIDUALS, 26 FIRST-EPISODE (FE) PSYCHOSIS INDIVIDUALS AND 30 CHRONIC SCHIZOPHRENIA (CS) INDIVIDUALS. THE POSITIVE AND NEGATIVE SYNDROME SCALE (PANSS) WAS USED TO ASSESS SCHIZOPHRENIA SEVERITY. AFTER PYROSEQUENCING SELECTED CPG SITES OF PERIPHERAL BLOOD, THE AVERAGE MEAN DNAM LEVELS WERE COMPARED AMONGST THE 4 SUBGROUPS. OUR RESULTS SHOWED DIFFERING LEVELS OF DNAM, WITH UHR HAVING THE LOWEST (7.72 +/- 0.19) WHILE THE CS HAD THE HIGHEST LEVELS (HC: 8.78 +/- 0.35; FE: 7.75 +/- 0.37; CS: 8.82 +/- 0.48). SIGNIFICANTLY HIGHER AVERAGE MEAN DNAM LEVELS WERE FOUND IN CS SUBJECTS ON AP (9.12 +/- 0.61) COMPARED TO UHR WITHOUT MEDICATION (UHR(-)) (7.39 +/- 0.18). A SIGNIFICANT ASSOCIATION WAS ALSO OBSERVED BETWEEN THE AVERAGE MEAN DNAM OF FE AND PANSS NEGATIVE SYMPTOM FACTOR (R(2) = 0.237, SS = -0.401, *P = 0.033). IN CONCLUSION, OUR FINDINGS SUGGESTED DIFFERENT LEVELS OF DNAM FOR SUBJECTS AT DIFFERENT STAGES OF PSYCHOSIS. THOSE SUBJECTS THAT TOOK AP HAVE DIFFERENT DNAM LEVELS. THERE WERE SIGNIFICANT ASSOCIATIONS BETWEEN FE DNAM AND NEGATIVE PANSS SCORES. WITH MORE FUTURE EXPERIMENTS AND ON LARGER COHORTS, THERE MAY BE POTENTIAL USE OF DNAM OF THE RELN GENE AS ONE OF THE GENES FOR THE BIOLOGICAL-BASED MARKER FOR SYMPTOM SEVERITY IN PSYCHOSIS. 2022 4 513 34 ASSOCIATION OF SEROTONIN TRANSPORTER GENE ALUJB METHYLATION WITH MAJOR DEPRESSION, AMYGDALA RESPONSIVENESS, 5-HTTLPR/RS25531 POLYMORPHISM, AND STRESS. DNA METHYLATION PROFILES OF THE SEROTONIN TRANSPORTER GENE (SLC6A4) HAVE BEEN SHOWN TO ALTER SLC6A4 EXPRESSION, DRIVE ANTIDEPRESSANT TREATMENT RESPONSE AND MODIFY BRAIN FUNCTIONS. THIS STUDY INVESTIGATED WHETHER METHYLATION OF AN ALUJB ELEMENT IN THE SLC6A4 PROMOTOR WAS ASSOCIATED WITH MAJOR DEPRESSIVE DISORDER (MDD), AMYGDALA REACTIVITY TO EMOTIONAL FACES, 5-HTTLPR/RS25531 POLYMORPHISM, AND RECENT STRESS. MDD PATIENTS (N=122) AND HEALTHY CONTROLS (HC, N=176) UNDERWENT FMRI DURING AN EMOTIONAL FACE-MATCHING TASK. INDIVIDUAL SLC6A4 ALUJB METHYLATION PROFILES WERE ASCERTAINED AND ASSOCIATED WITH MDD, AMYGDALA REACTIVITY, 5-HTTLPR/RS25531, AND STRESS. SLC6A4 ALUJB METHYLATION WAS SIGNIFICANTLY LOWER IN MDD COMPARED TO HC AND IN STRESSED COMPARED TO LESS STRESSED PARTICIPANTS. LOWER ALUJB METHYLATION WAS PARTICULARLY FOUND IN 5-HTTLPR/RS25531 RISK ALLELE CARRIERS UNDER STRESS AND CORRELATED WITH LESS DEPRESSIVE EPISODES. FMRI ANALYSIS REVEALED A SIGNIFICANT INTERACTION OF ALUJB METHYLATION AND DIAGNOSIS IN THE AMYGDALA, WITH MDD PATIENTS SHOWING LOWER ALUJB METHYLATION ASSOCIATED WITH DECREASED AMYGDALA REACTIVITY. WHILE NO JOINT EFFECT OF ALUJB METHYLATION AND 5-HTTLPR/RS25531 EXISTED, RISK ALLELE CARRIERS SHOWED SIGNIFICANTLY INCREASED BILATERAL AMYGDALA ACTIVATION. THESE FINDINGS SUGGEST A ROLE OF SLC6A4 ALUJB METHYLATION IN MDD, AMYGDALA REACTIVITY, AND STRESS REACTION, PARTLY INTERWOVEN WITH 5-HTTLPR/RS25531 EFFECTS. PATIENTS WITH LOW METHYLATION IN CONJUNCTION WITH A SHORTER MDD HISTORY AND DECREASED AMYGDALA REACTIVITY MIGHT FEATURE A MORE STRESS-ADAPTIVE EPIGENETIC PROCESS, MAYBE VIA THEORETICALLY POSSIBLE ENDOGENOUS ANTIDEPRESSANT-LIKE EFFECTS. IN CONTRAST, PATIENTS WITH HIGHER METHYLATION MIGHT POSSIBLY SUFFER FROM IMPAIRED EPIGENETIC ADAPTION TO CHRONIC STRESS. FURTHER, THE 5-HTTLPR/RS25531 ASSOCIATION WITH AMYGDALA ACTIVATION WAS CONFIRMED IN OUR LARGE SAMPLE. 2018 5 1810 27 EFFECTS OF ANTIPSYCHOTICS ON THE BDNF IN SCHIZOPHRENIA. BRAIN-DERIVED NEUROTROPIC FACTOR (BDNF) IS INVOLVED IN THE DEVELOPMENT OF THE BRAIN, AND LIKELY INFLUENCES THE NEUROPLASTICITY IN SCHIZOPHRENIA. BDNF IS ALSO BELIEVED TO INTERACT WITH OTHER NEUROTRANSMITTER SYSTEMS IMPLICATED IN SCHIZOPHRENIA, SUCH AS DOPAMINE, GLUTAMATE, SEROTONIN AND GABA. THEREFORE, BDNF IS A CANDIDATE GENE FOR SCHIZOPHRENIA. IN PAST DECADES, THE BLOOD (SERUM OR PLASMA) BDNF PROTEIN LEVELS AND BDNF GENE ALLELES AND GENOTYPES TO THE CLINICAL FEATURES OF SCHIZOPHRENIA, SUCH AS AGE OF ONSET, CLINICAL SUBTYPES, SYMPTOM SEVERITY, AND DRUG RESPONSE, HAVE BEEN EVALUATED AMONG DIFFERENT POPULATIONS. HOWEVER, THE RESULTS ARE STILL INCONSISTENT. FURTHER, DIFFERENT DRUGS HAVE BEEN REPORTED TO HAVE DIFFERENT EFFECTS ON BDNF PROTEIN LEVELS. A CROSS-SECTIONAL SURVEY REVEALED THAT SERUM BDNF LEVELS IN CHRONIC SCHIZOPHRENIC PATIENTS TREATED WITH CLOZAPINE EXCEEDED THOSE OF PATIENTS TREATED WITH RISPERIDONE OR WITH TYPICAL ANTIPSYCHOTICS. IN RECENT TIMES, BDNF EPIGENETIC STUDIES HAVE ALSO BEEN CONDUCTED IN CLINICAL STUDIES OF SCHIZOPHRENIA TO ADDRESS THE QUESTION OF WHY PATIENTS WITH THE SAME GENE GENOTYPE AND ALLELES HAVE DIFFERENT CLINICAL PRESENTATIONS. IN ADDITION, THE EFFECTS OF DIFFERENT ANTIPSYCHOTIC DRUGS ON GENE METHYLATION AND PROTEIN ACETYLATION HAVE ALSO BEEN REPORTED. IN CONCLUSION, MORE DATA ARE NEEDED REGARDING BDNF IN THE BRAIN AND IN PERIPHERAL BLOOD, INCLUDING PROTEIN LEVELS, SINGLE NUCLEOTIDE POLYMORPHISMS, EPIGENETIC REGULATION, AND CLINICAL DATA IN ORDER TO UNDERSTAND THE ROLE OF BDNF IN SCHIZOPHRENIA. 2013 6 3133 38 GLOBAL DNA HYPOMETHYLATION AND ITS CORRELATION TO THE BETAINE LEVEL IN PERIPHERAL BLOOD OF PATIENTS WITH SCHIZOPHRENIA. ACCUMULATING EVIDENCE SUGGESTS THAT ABERRANT EPIGENETIC REGULATION IS INVOLVED IN THE PATHOPHYSIOLOGY OF MAJOR PSYCHIATRIC DISORDERS SUCH AS SCHIZOPHRENIA (SZ) AND BIPOLAR DISORDER (BD). WE PREVIOUSLY SHOWED THAT THE PLASMA LEVEL OF BETAINE (N,N,N-TRIMETHYLGLYCINE), A METHYL-GROUP DONOR, WAS SIGNIFICANTLY DECREASED IN PATIENTS WITH FIRST EPISODE SCHIZOPHRENIA (FESZ). IN THIS STUDY, WE IDENTIFIED DECREASE OF GLOBAL DNA METHYLATION LEVEL IN FESZ (N = 24 PATIENTS VS N = 42 CONTROLS), AND FOUND THAT GLOBAL DNA METHYLATION LEVEL WAS INVERSELY CORRELATED WITH SCORES ON THE GLOBAL ASSESSMENT OF FUNCTIONING (GAF) SCALE, AND POSITIVELY CORRELATED WITH PLASMA BETAINE LEVEL. NOTABLY, CORRELATIONS BETWEEN LEVELS OF BETAINE AND ITS METABOLITES (N,N-DIMETHYLGLYCINE AND SARCOSINE, N-METHYLGLYCINE) WERE LOWER OR LOST IN FESZ PLASMA, BUT REMAINED HIGH IN CONTROLS. WE FURTHER EXAMINED GLOBAL DNA METHYLATION LEVELS IN PATIENTS WITH CHRONIC SZ (N = 388) AND BD (N = 414) AS WELL AS CONTROLS (N = 430), AND CONFIRMED SIGNIFICANT HYPOMETHYLATION AND DECREASED BETAINE LEVEL IN SZ. WE ALSO FOUND THAT PATIENTS WITH BD TYPE I, BUT NOT THOSE WITH BD TYPE II, SHOWED SIGNIFICANT GLOBAL HYPOMETHYLATION. THESE RESULTS SUGGEST THAT GLOBAL HYPOMETHYLATION ASSOCIATED WITH DECREASED BETAINE LEVEL IN BLOOD CELLS IS COMMON TO SZ AND BD, AND MAY REFLECT COMMON PATHOPHYSIOLOGY SUCH AS PSYCHOTIC SYMPTOMS. 2020 7 1299 33 DECREASED REELIN EXPRESSION IN THE LEFT PREFRONTAL CORTEX (BA9) IN CHRONIC SCHIZOPHRENIA PATIENTS. BACKGROUND: REELIN IS UNDER EPIGENETIC CONTROL AND HAS BEEN REPORTED TO BE DECREASED IN CORTICAL REGIONS IN SCHIZOPHRENIA. METHODS: TO ESTABLISH IF EXPRESSION OF REELIN IS ALTERED IN SPECIFIC CORTICAL, HIPPOCAMPAL OR THALAMIC REGIONS OF SCHIZOPHRENIA PATIENTS, WE MEASURED GENE EXPRESSION OF REELIN IN A POSTMORTEM STUDY OF ELDERLY PATIENTS WITH SCHIZOPHRENIA AND NON-AFFECTED CONTROLS IN BOTH HEMISPHERES DIFFERENTIATING BETWEEN GRAY AND WHITE MATTER. WE COMPARED CEREBRAL POSTMORTEM SAMPLES (DORSOLATERAL PREFRONTAL CORTEX BA9 AND BA46, SUPERIOR TEMPORAL CORTEX BA22, ENTORHINAL CORTEX BA28, SENSORIC CORTEX BA1-3, HIPPOCAMPUS, CA4, MEDIODORSAL NUCLEUS OF THE THALAMUS) FROM 12 SCHIZOPHRENIA PATIENTS WITH 13 NORMAL SUBJECTS INVESTIGATING GENE EXPRESSION OF REELIN IN THE GRAY AND WHITE MATTER OF BOTH HEMISPHERES BY IN SITU-HYBRIDIZATION. RESULTS: THE LEFT PREFRONTAL AREA (BA9) OF SCHIZOPHRENIA PATIENTS REVEALED A DECREASED EXPRESSION OF REELIN-MRNA OF 29.1% IN THE WHITE (P = 0.022) AND 13.6% IN THE GRAY MATTER (P = 0.007) COMPARED TO THE CONTROL GROUP. NONE OF THE OTHER REGIONS EXAMINED SHOWED ANY STATISTICALLY SIGNIFICANT DIFFERENCES. CONCLUSION: SINCE REELIN IS RESPONSIBLE FOR MIGRATION AND SYNAPSE FORMATION, THE DECREASED GENE EXPRESSION OF REELIN IN THE LEFT PREFRONTAL AREA OF SCHIZOPHRENIA PATIENTS POINTS TO NEURODEVELOPMENTAL DEFICITS IN NEURONAL MIGRATION AND SYNAPTIC PLASTICITY. HOWEVER, OUR STUDY GROUP WAS SMALL, AND RESULTS SHOULD BE VERIFIED USING LARGER SAMPLES. 2012 8 173 51 ACCELERATED AGING IN BIPOLAR DISORDERS: AN EXPLORATORY STUDY OF SIX EPIGENETIC CLOCKS. BIPOLAR DISORDER (BD) IS A CHRONIC AND SEVERE PSYCHIATRIC DISORDER ASSOCIATED WITH SIGNIFICANT MEDICAL MORBIDITY AND REDUCED LIFE EXPECTANCY. IN THIS STUDY, WE ASSESSED ACCELERATED EPIGENETIC AGING IN INDIVIDUALS WITH BD USING VARIOUS DNA METHYLATION (DNAM)-BASED MARKERS. FOR THIS PURPOSE, WE USED FIVE EPIGENETIC CLOCKS (HORVATH, HANNUM, EN, PHENOAGE, AND GRIMAGE) AND A DNAM-BASED TELOMERE LENGTH CLOCK (DNAMTL). DNAM PROFILES WERE OBTAINED USING INFINIUM METHYLATIONEPIC ARRAYS FROM WHOLE-BLOOD SAMPLES OF 184 INDIVIDUALS WITH BD. WE ALSO ESTIMATED BLOOD CELL COUNTS BASED ON DNAM LEVELS FOR ADJUSTMENT. SIGNIFICANT CORRELATIONS BETWEEN CHRONOLOGICAL AGE AND EACH EPIGENETIC AGE ESTIMATED USING THE SIX DIFFERENT CLOCKS WERE OBSERVED. FOLLOWING ADJUSTMENT FOR BLOOD CELL COUNTS, WE FOUND THAT THE SIX EPIGENETIC AGEACCELS (AGE ACCELERATIONS) WERE SIGNIFICANTLY ASSOCIATED WITH THE BODY MASS INDEX. GRIMAGE AGEACCEL WAS SIGNIFICANTLY ASSOCIATED WITH MALE SEX, SMOKING STATUS AND CHILDHOOD MALTREATMENT. DNAMTL AGEACCEL WAS SIGNIFICANTLY ASSOCIATED WITH SMOKING STATUS. OVERALL, THIS STUDY SHOWED THAT DISTINCT EPIGENETIC CLOCKS ARE SENSITIVE TO DIFFERENT ASPECTS OF AGING PROCESS IN BD. FURTHER INVESTIGATIONS WITH COMPREHENSIVE EPIGENETIC CLOCK ANALYSES AND LARGE SAMPLES ARE REQUIRED TO CONFIRM OUR FINDINGS OF POTENTIAL DETERMINANTS OF AN ACCELERATED EPIGENETIC AGING IN BD. 2023 9 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 10 525 36 ASSOCIATIONS OF BODY COMPOSITION AND PHYSICAL ACTIVITY LEVEL WITH MULTIPLE MEASURES OF EPIGENETIC AGE ACCELERATION. EPIGENETIC CLOCKS USE DNA METHYLATION TO ESTIMATE BIOLOGICAL AGE. WHETHER BODY COMPOSITION AND PHYSICAL ACTIVITY ARE ASSOCIATED WITH THESE CLOCKS IS NOT WELL UNDERSTOOD. USING BLOOD SAMPLES COLLECTED AT ENROLLMENT (2003-2009) FROM 2,758 WOMEN IN THE US NATIONWIDE SISTER STUDY, WE CALCULATED 6 EPIGENETIC AGE ACCELERATION METRICS USING 4 EPIGENETIC CLOCKS (HANNUM, HORVATH, PHENOAGE, GRIMAGE). RECREATIONAL PHYSICAL ACTIVITY WAS SELF-REPORTED, AND ADIPOSITY MEASURES WERE ASSESSED BY TRAINED MEDICAL EXAMINERS (BODY MASS INDEX (BMI), WAIST-TO-HIP RATIO (WTH), WAIST CIRCUMFERENCE). IN CROSS-SECTIONAL ANALYSES, ALL ADIPOSITY MEASURES WERE ASSOCIATED WITH EPIGENETIC AGE ACCELERATION. THE STRONGEST ASSOCIATION WAS FOR BMI AND PHENOAGE, A MEASURE OF BIOLOGICAL AGE THAT CORRELATES WITH CHRONIC DISEASE (BMI OF >/=35.0 VS. 18.5-24.9, BETA = 3.15 YEARS, 95% CONFIDENCE INTERVAL (CI): 2.41, 3.90; P FOR TREND < 0.001). IN A MUTUAL-ADJUSTMENT MODEL, BOTH WERE ASSOCIATED WITH PHENOAGE AGE ACCELERATION (BMI OF >/=35.0 VS. 18.5-24.9, BETA = 2.69 YEARS, 95% CI: 1.90, 3.48; P FOR TREND < 0.001; QUARTILE 4 VS.1 WTH, BETA = 1.00 YEARS, 95% CI: 0.34, 1.65; P FOR TREND < 0.008). AFTER ADJUSTMENT, PHYSICAL ACTIVITY WAS ASSOCIATED ONLY WITH GRIMAGE (QUARTILE 4 VS. 1, BETA = -0.42 YEARS, 95% CI: -0.70, -0.14; P FOR TREND = 0.001). PHYSICAL ACTIVITY ATTENUATED THE WAIST CIRCUMFERENCE ASSOCIATIONS WITH PHENOAGE AND GRIMAGE. EXCESS ADIPOSITY WAS ASSOCIATED WITH EPIGENETIC AGE ACCELERATION; PHYSICAL ACTIVITY MIGHT ATTENUATE ASSOCIATIONS WITH WAIST CIRCUMFERENCE. 2021 11 659 38 BLOOD GLOBAL DNA METHYLATION IS DECREASED IN NON-SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) PATIENTS. BACKGROUND: ALTERATIONS IN GLOBAL DNA METHYLATION HAVE BEEN ASSOCIATED WITH OXIDATIVE STRESS (OS). SINCE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS CHARACTERIZED BY INCREASED OXIDATIVE STRESS WE AIMED TO EVALUATE THE LEVELS OF GLOBAL DNA METHYLATION IN THIS PATIENT GROUP. METHODS: WE ASSESSED METHYLCYTOSINE (MCYT) LEVELS IN DNA FROM BLOOD COLLECTED IN 43 COPD PATIENTS (29 WITH MILD AND 14 WITH MODERATE DISEASE) AND 43 AGE- AND SEX-MATCHED HEALTHY CONTROLS. RESULTS: DNA METHYLATION WAS SIGNIFICANTLY LOWER IN COPD PATIENTS VS. CONTROLS (4.20 +/- 0.18% MCYT VS. 4.29 +/- 0.18% MCYT, P = 0.02). FURTHERMORE, DNA METHYLATION IN COPD PATIENTS WITH MODERATE DISEASE WAS SIGNIFICANTLY LOWER THAN THAT IN PATIENTS WITH MILD DISEASE (4.14 +/- 0.15% MCYT VS. 4.23 +/- 0.19% MCYT, P < 0.05). UNIVARIATE LOGISTIC REGRESSION ANALYSIS SHOWED THAT LOWER DNA METHYLATION LEVELS WERE ASSOCIATED WITH PRESENCE OF COPD (CRUDE OR = 0.06, 95% CI 0.00 TO 0.67, P = 0.023). THIS RELATIONSHIP REMAINED SIGNIFICANT AFTER ADJUSTING FOR SEVERAL CONFOUNDERS (OR 0.03, 95% CI 0.00 TO 0.67; P = 0.028). RECEIVER OPERATING CHARACTERISTICS (ROC) CURVE ANALYSIS DEMONSTRATED THE AREA UNDER THE CURVE OF MCYT WAS 0.646, WITH 46.6% SENSITIVITY AND 79.1% SPECIFICITY FOR PRESENCE OF COPD. CONCLUSIONS: THERE WERE NO SIGNIFICANT CORRELATIONS BETWEEN METHYLATION AND OS INDICES. THE PRESENCE AND SEVERITY OF COPD IS ASSOCIATED WITH PROGRESSIVELY LOWER DNA METHYLATION IN BLOOD. HOWEVER, THIS EPIGENETIC ALTERATION SEEMS INDEPENDENT OF OXIDATIVE STRESS. 2017 12 3416 34 HTR1A, HTR1B, HTR2A, HTR2C AND HTR6 GENE POLYMORPHISMS AND EXTRAPYRAMIDAL SIDE EFFECTS IN HALOPERIDOL-TREATED PATIENTS WITH SCHIZOPHRENIA. SCHIZOPHRENIA IS A SERIOUS, CHRONIC PSYCHIATRIC DISORDER REQUIRING LIFELONG TREATMENT. EXTRAPYRAMIDAL SIDE EFFECTS (EPS) ARE COMMON ADVERSE REACTIONS TO ANTIPSYCHOTIC MEDICATIONS. IN ADDITION TO THE DOPAMINERGIC SYSTEM, SEROTONERGIC MECHANISMS, INCLUDING SEROTONIN (5-HT) RECEPTORS, MIGHT BE INVOLVED IN EPS DEVELOPMENT. THIS STUDY AIMED TO EXAMINE MOLECULAR ASSOCIATIONS OF HTR1A, HTR1B, HTR2A, HTR2C AND HTR6 GENE POLYMORPHISMS WITH ACUTE EPS IN 229 MALE SCHIZOPHRENIA PATIENTS, FOLLOWING TWO WEEKS OF HALOPERIDOL MONOTHERAPY. THE SIMPSON-ANGUS RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS (SAS), BARNES AKATHISIA RATING SCALE (BARS) AND EXTRAPYRAMIDAL SYMPTOM RATING SCALE (ESRS) WERE USED TO EVALUATE EPS SEVERITY. GENOTYPING WAS PERFORMED USING REAL-TIME PCR, FOLLOWING EXTRACTION OF BLOOD DNA. SIGNIFICANT ACUTE EPS APPEARED IN 48.03% OF SCHIZOPHRENIA PATIENTS. FOR THE RS13212041 HTR1B GENE POLYMORPHISM, AFFECTING MICRORNA REGULATION OF HTR1B GENE EXPRESSION, A HIGHER FREQUENCY OF TT CARRIERS WAS FOUND AMONG HALOPERIDOL-TREATED PATIENTS WITH AKATHISIA WHEN COMPARED TO THE GROUP WITHOUT AKATHISIA SYMPTOMS. IN COMPARISON TO C-ALLELE CARRIERS, PATIENTS CARRYING THE TT GENOTYPE HAD HIGHER AKATHISIA SEVERITY, AS DETERMINED BY THE SAS, BARS AND ESRS SCALES. THESE MOLECULAR FINDINGS SUGGEST POTENTIAL INVOLVEMENT OF 5-HT(1B) RECEPTORS IN AKATHISIA DEVELOPMENT FOLLOWING HALOPERIDOL TREATMENT, AS WELL AS POSSIBLE EPIGENETIC MECHANISMS OF SEROTONERGIC MODULATION ASSOCIATED WITH ANTIPSYCHOTIC-INDUCED EPS. 2020 13 6250 35 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 14 5273 38 PROMOTER METHYLATION AND BDNF AND DAT1 GENE EXPRESSION PROFILES IN PATIENTS WITH DRUG ADDICTION. BACKGROUND: DRUG ADDICTION IS A BRAIN DISORDER THAT HAS NEGATIVE CONSEQUENCES FOR INDIVIDUALS AND SOCIETY. ADDICTIONS ARE CHRONIC RELAPSING DISEASES OF THE BRAIN THAT ARE CAUSED BY DIRECT DRUG-INDUCED EFFECTS AND PERSEVERING NEUROADAPTATIONS AT THE EPIGENETIC, NEUROPEPTIDE AND NEUROTRANSMITTER LEVELS. BECAUSE THE DOPAMINERGIC SYSTEM HAS A SIGNIFICANT ROLE IN DRUG ABUSE, THE PURPOSE OF THIS STUDY WAS TO ANALYZE THE METHYLATION AND EXPRESSION PROFILE OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND DOPAMINE TRANSPORTER (DAT1) GENES IN INDIVIDUALS WITH DRUG ADDICTION. MATERIALS AND METHODS: BDNF AND DAT1 PROMOTER METHYLATION WERE INVESTIGATED WITH A METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION (PCR) TECHNIQUE IN BLOOD SAMPLES FROM 75 INDIVIDUALS WITH DRUG ADDICTION AND 65 HEALTHY CONTROLS. THE EXPRESSION LEVELS OF BDNF AND DAT1 WERE ASSESSED IN 12 MRNA SAMPLES FROM THE BLOOD OF PATIENTS AND COMPARED TO THE SAMPLES OF HEALTHY CONTROLS (N = 12) WITH REAL-TIME QUANTITATIVE REVERSE TRANSCRIPTION PCR. RESULTS: NO SIGNIFICANT DIFFERENCES WERE FOUND IN THE METHYLATION OF BDNF AND DAT1 BETWEEN PATIENTS AND CONTROLS, BUT THE RELATIVE LEVELS OF EXPRESSION OF BDNF AND DAT1 MRNA DIFFERED SIGNIFICANTLY IN THE PATIENTS COMPARED TO CONTROLS (P < 0.0001). CONCLUSION: THESE RESULTS SHOWED THAT THE METHYLATION STATUS OF THE BDNF AND DAT1 GENES HAD NO SIGNIFICANT FUNCTION IN THE PROCESSES OF DRUG ADDICTION. 2015 15 1645 45 DOES THE EPIGENETIC CLOCK GRIMAGE PREDICT MORTALITY INDEPENDENT OF GENETIC INFLUENCES: AN 18 YEAR FOLLOW-UP STUDY IN OLDER FEMALE TWIN PAIRS. BACKGROUND: EPIGENETIC CLOCKS ARE BASED ON DNA METHYLATION (DNAM). IT HAS BEEN SUGGESTED THAT THESE CLOCKS ARE USEABLE MARKERS OF BIOLOGICAL AGING AND PREMATURE MORTALITY. BECAUSE GENETIC FACTORS EXPLAIN VARIATIONS IN BOTH EPIGENETIC AGING AND MORTALITY, THIS ASSOCIATION COULD ALSO BE EXPLAINED BY SHARED GENETIC FACTORS. WE INVESTIGATED THE INFLUENCE OF GENETIC AND LIFESTYLE FACTORS (SMOKING, ALCOHOL CONSUMPTION, PHYSICAL ACTIVITY, CHRONIC DISEASES, BODY MASS INDEX) AND EDUCATION ON THE ASSOCIATION OF ACCELERATED EPIGENETIC AGING WITH MORTALITY USING A LONGITUDINAL TWIN DESIGN. UTILIZING A PUBLICLY AVAILABLE ONLINE TOOL, WE CALCULATED THE EPIGENETIC AGE USING TWO EPIGENETIC CLOCKS, HORVATH DNAMAGE AND DNAM GRIMAGE, IN 413 FINNISH TWIN SISTERS, AGED 63-76 YEARS, AT THE BEGINNING OF THE 18-YEAR MORTALITY FOLLOW-UP. EPIGENETIC AGE ACCELERATION WAS CALCULATED AS THE RESIDUALS FROM A LINEAR REGRESSION MODEL OF EPIGENETIC AGE ESTIMATED ON CHRONOLOGICAL AGE (AA(HORVATH), AA(GRIMAGE), RESPECTIVELY). COX PROPORTIONAL HAZARD MODELS WERE CONDUCTED FOR INDIVIDUALS AND TWIN PAIRS. RESULTS: THE RESULTS OF THE INDIVIDUAL-BASED ANALYSES SHOWED AN INCREASED MORTALITY HAZARD RATIO (HR) OF 1.31 (CI(95): 1.13-1.53) PER ONE STANDARD DEVIATION (SD) INCREASE IN AA(GRIMAGE). THE RESULTS INDICATED NO SIGNIFICANT ASSOCIATIONS OF AA(HORVATH) WITH MORTALITY. PAIRWISE MORTALITY ANALYSES SHOWED AN HR OF 1.50 (CI(95): 1.02-2.20) PER 1 SD INCREASE IN AA(GRIMAGE). HOWEVER, AFTER ADJUSTING FOR SMOKING, THE HR ATTENUATED SUBSTANTIALLY AND WAS STATISTICALLY NON-SIGNIFICANT (1.29; CI(95): 0.84-1.99). SIMILARLY, IN MULTIVARIABLE ADJUSTED MODELS THE HR (1.42-1.49) WAS NON-SIGNIFICANT. IN AA(HORVATH), THE NON-SIGNIFICANT HRS WERE LOWER AMONG MONOZYGOTIC PAIRS IN COMPARISON TO DIZYGOTIC PAIRS, WHILE IN AA(GRIMAGE) THERE WERE NO SYSTEMATIC DIFFERENCES BY ZYGOSITY. FURTHER, THE PAIRWISE ANALYSIS IN QUARTILES SHOWED THAT THE INCREASED WITHIN PAIR DIFFERENCE IN AA(GRIMAGE) WAS ASSOCIATED WITH A HIGHER ALL-CAUSE MORTALITY RISK. CONCLUSIONS: IN CONCLUSION, THE FINDINGS SUGGEST THAT DNAM GRIMAGE IS A STRONG PREDICTOR OF MORTALITY INDEPENDENT OF GENETIC INFLUENCES. SMOKING, WHICH IS KNOWN TO ALTER DNAM LEVELS AND IS BUILT INTO THE DNAM GRIMAGE ALGORITHM, ATTENUATED THE ASSOCIATION BETWEEN EPIGENETIC AGING AND MORTALITY RISK. 2021 16 1512 34 DNA METHYLATION AND PROTEIN MARKERS OF CHRONIC INFLAMMATION AND THEIR ASSOCIATIONS WITH BRAIN AND COGNITIVE AGING. BACKGROUND AND OBJECTIVES: TO INVESTIGATE CHRONIC INFLAMMATION IN RELATION TO COGNITIVE AGING BY COMPARISON OF AN EPIGENETIC AND SERUM BIOMARKER OF C-REACTIVE PROTEIN AND THEIR ASSOCIATIONS WITH NEUROIMAGING AND COGNITIVE OUTCOMES. METHODS: AT BASELINE, PARTICIPANTS (N = 521) WERE COGNITIVELY NORMAL, AROUND 73 YEARS OF AGE (MEAN 72.4, SD 0.716), AND HAD INFLAMMATION, VASCULAR RISK (CARDIOVASCULAR DISEASE HISTORY, HYPERTENSION, DIABETES, SMOKING, ALCOHOL CONSUMPTION, BODY MASS INDEX), AND NEUROIMAGING (STRUCTURAL AND DIFFUSION MRI) DATA AVAILABLE. BASELINE INFLAMMATORY STATUS WAS QUANTIFIED BY A TRADITIONAL MEASURE OF PERIPHERAL INFLAMMATION-SERUM C-REACTIVE PROTEIN (CRP)-AND AN EPIGENETIC MEASURE (DNA METHYLATION [DNAM] SIGNATURE OF CRP). LINEAR MODELS WERE USED TO EXAMINE THE INFLAMMATION-BRAIN HEALTH ASSOCIATIONS; MEDIATION ANALYSES WERE PERFORMED TO INTERROGATE THE RELATIONSHIP BETWEEN CHRONIC INFLAMMATION, BRAIN STRUCTURE, AND COGNITIVE FUNCTIONING. RESULTS: WE DEMONSTRATE THAT DNAM CRP SHOWS SIGNIFICANTLY (ON AVERAGE 6.4-FOLD) STRONGER ASSOCIATIONS WITH BRAIN HEALTH OUTCOMES THAN SERUM CRP. DNAM CRP IS ASSOCIATED WITH TOTAL BRAIN VOLUME (BETA = -0.197, 95% CONFIDENCE INTERVAL [CI] -0.28 TO -0.12, P (FDR) = 8.42 X 10(-6)), GRAY MATTER VOLUME (BETA = -0.200, 95% CI -0.28 TO -0.12, P (FDR) = 1.66 X 10(-5)), AND WHITE MATTER VOLUME (BETA = -0.150, 95% CI -0.23 TO -0.07, P (FDR) = 0.001) AND REGIONAL BRAIN ATROPHY. WE ALSO FIND THAT DNAM CRP HAS AN INVERSE ASSOCIATION WITH GLOBAL AND DOMAIN-SPECIFIC (SPEED, VISUOSPATIAL, AND MEMORY) COGNITIVE FUNCTIONING AND THAT BRAIN STRUCTURE PARTIALLY MEDIATES THIS CRP-COGNITIVE ASSOCIATION (UP TO 29.7%), DEPENDENT ON LIFESTYLE AND HEALTH FACTORS. DISCUSSION: THESE RESULTS SUPPORT THE HYPOTHESIS THAT CHRONIC INFLAMMATION MAY CONTRIBUTE TO NEURODEGENERATIVE BRAIN CHANGES THAT UNDERLIE DIFFERENCES IN COGNITIVE ABILITY IN LATER LIFE AND HIGHLIGHT THE POTENTIAL OF DNAM PROXIES FOR INDEXING CHRONIC INFLAMMATORY STATUS. CLASSIFICATION OF EVIDENCE: THIS STUDY PROVIDES CLASS II EVIDENCE THAT A DNAM SIGNATURE OF CRP LEVELS IS MORE STRONGLY ASSOCIATED WITH BRAIN HEALTH OUTCOMES THAN SERUM CRP LEVELS. 2021 17 5957 35 TELOMERE LENGTH AND EPIGENETIC AGE ACCELERATION IN ADOLESCENTS WITH ANXIETY DISORDERS. EVIDENCE ON THE RELATIONSHIP BETWEEN GENETICS AND MENTAL HEALTH ARE FLOURISHING. HOWEVER, FEW STUDIES ARE EVALUATING EARLY BIOMARKERS THAT MIGHT LINK GENES, ENVIRONMENT, AND PSYCHOPATHOLOGY. WE AIMED TO STUDY TELOMERE LENGTH (TL) AND EPIGENETIC AGE ACCELERATION (AA) IN A COHORT OF ADOLESCENTS WITH AND WITHOUT ANXIETY DISORDERS (N = 234). WE EVALUATED A REPRESENTATIVE SUBSAMPLE OF PARTICIPANTS AT BASELINE AND AFTER 5 YEARS (N = 76) AND CATEGORIZED THEM ACCORDING TO THEIR ANXIETY DISORDER DIAGNOSIS AT BOTH TIME POINTS: (1) CONTROL GROUP (NO ANXIETY DISORDER, N = 18), (2) VARIABLE GROUP (ANXIETY DISORDER IN ONE EVALUATION, N = 38), AND (3) PERSISTENT GROUP (ANXIETY DISORDER AT BOTH TIME POINTS, N = 20). WE ASSESSED RELATIVE MEAN TL BY REAL-TIME QUANTITATIVE PCR AND DNA METHYLATION BY INFINIUM HUMANMETHYLATION450 BEADCHIP. WE CALCULATED AA USING THE HORVATH AGE ESTIMATION ALGORITHM AND ANALYZED DIFFERENCES AMONG GROUPS USING GENERALIZED LINEAR MIXED MODELS. THE PERSISTENT GROUP OF ANXIETY DISORDER DID NOT CHANGE TL OVER TIME (P = 0.495). THE VARIABLE GROUP HAD HIGHER BASELINE TL (P = 0.003) BUT NO ACCELERATED TL EROSION IN COMPARISON TO THE NON-ANXIETY CONTROL GROUP (P = 0.053). FURTHERMORE, THERE WERE NO DIFFERENCES IN AA AMONG GROUPS OVER TIME. OUR FINDINGS SUGGEST THAT ADOLESCENTS WITH CHRONIC ANXIETY DID NOT CHANGE TELOMERE LENGTH OVER TIME, WHICH COULD BE RELATED TO A DELAY IN NEURONAL DEVELOPMENT IN THIS PERIOD OF LIFE. 2021 18 1513 31 DNA METHYLATION AND PSYCHOTHERAPY RESPONSE IN TRAUMA-EXPOSED MEN WITH APPETITIVE AGGRESSION. EXPOSURE TO VIOLENCE CAN LEAD TO APPETITIVE AGGRESSION (AA), THE POSITIVE FEELING AND FASCINATION ASSOCIATED WITH VIOLENCE, AND POSTTRAUMATIC STRESS DISORDER (PTSD), CHARACTERISED BY HYPERAROUSAL, REEXPERIENCE AND FEELINGS OF ONGOING THREAT. PSYCHOTHERAPEUTIC INTERVENTIONS MAY ACT VIA DNA METHYLATION, AN ENVIRONMENTALLY SENSITIVE EPIGENETIC MECHANISM THAT CAN INFLUENCE GENE EXPRESSION. WE INVESTIGATED EPIGENETIC SIGNATURES OF PSYCHOTHERAPY FOR PTSD AND AA SYMPTOMS IN SOUTH AFRICAN MEN WITH CHRONIC TRAUMA EXPOSURE. PARTICIPANTS WERE ASSIGNED TO ONE OF THREE GROUPS: NARRATIVE EXPOSURE THERAPY FOR FORENSIC OFFENDER REHABILITATION (FORNET), COGNITIVE BEHAVIOURAL THERAPY OR WAITING LIST CONTROL (N = 9-10/GROUP). PARTICIPANTS PROVIDED SALIVA AND COMPLETED THE APPETITIVE AGGRESSION SCALE AND PTSD SYMPTOM SEVERITY INDEX AT BASELINE, 8-MONTH AND 16-MONTH FOLLOW-UP. THE RELATIONSHIP, OVER TIME, BETWEEN METHYLATION IN 22 GENE PROMOTER REGION SITES, SYMPTOM SCORES, AND TREATMENT WAS ASSESSED USING LINEAR MIXED MODELS. COMPARED TO BASELINE, PTSD AND AA SYMPTOM SEVERITY WERE SIGNIFICANTLY REDUCED AT 8 AND 16 MONTHS, RESPECTIVELY, IN THE FORNET GROUP. INCREASED METHYLATION OF GENES IMPLICATED IN DOPAMINERGIC NEUROTRANSMISSION (NR4A2) AND SYNAPTIC PLASTICITY (AUTS2) WAS ASSOCIATED WITH REDUCED PTSD SYMPTOM SEVERITY IN PARTICIPANTS RECEIVING FORNET. ANALYSES ACROSS PARTICIPANTS REVEALED A PROPORTIONAL RELATIONSHIP BETWEEN AA AND METHYLATION OF TFAM, A GENE INVOLVED IN MITOCHONDRIAL BIOSYNTHESIS. 2021 19 5700 35 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 20 4447 32 MOLECULAR MARKERS OF AGING, EXERCISE CAPACITY, & PHYSICAL ACTIVITY IN COPD. BACKGROUND: EXERCISE CAPACITY (EC) AND PHYSICAL ACTIVITY (PA) ARE INDEPENDENT, POTENTIALLY MODIFIABLE PREDICTORS OF CLINICAL OUTCOMES IN COPD. MOLECULAR MEASURES OF BIOLOGICAL AGE MAY HELP CHARACTERIZE VARIABILITY IN EC AND PA OBSERVED AMONG COPD PATIENTS. METHODS: VETERANS WITH COPD (FEV(1)/FVC<0.7 OR EMPHYSEMA ON CHEST COMPUTED TOMOGRAPHY) ENROLLED IN 2 COHORTS AT VA BOSTON COMPLETED QUESTIONNAIRES, A 6-MIN WALK DISTANCE (6MWD) FOR EC, AND BLOOD COLLECTION AT ENROLLMENT. PA DATA (AVERAGE DAILY STEP COUNT) WAS COLLECTED USING AN HJ-720 ITC PEDOMETER OVER >/=5 DAYS. A SUBSET OF SUBJECTS RETURNED FOR REPEAT ASSESSMENT AFTER 12 WEEKS. DNA METHYLATION DATA WAS GENERATED USING THE HUMANMETHYLATIONEPIC PLATFORM; EPIGENETIC ESTIMATES OF BIOLOGICAL AGE AND AGE ACCELERATION WERE GENERATED USING ESTABLISHED ALGORITHMS. MULTIVARIABLE MODELS EXAMINED THE ASSOCIATIONS BETWEEN BIOLOGICAL AGE, 6MWD, PA AND FUTURE ACUTE EXACERBATIONS (AES), ADJUSTING FOR CHRONOLOGICAL AGE, SEX, RACE, SMOKING STATUS, PACK-YEARS, BODY MASS INDEX, COHORT, AND ESTIMATED CELL COUNTS. RESULTS: SUBJECTS (N = 269) WERE PREDOMINANTLY MALE (98.5%), WHITE (92.9%), AND ELDERLY (70.6 +/- 8.5 YEARS) WITH AVERAGE FEV(1)% OF 57.7 +/- 21.1, 6MWD OF 374.3 +/- 93.5 M, AND DAILY STEPS OF 3043.4 +/- 2374 AT BASELINE. IN ADJUSTED MODELS, MULTIPLE MEASURES OF BASELINE EPIGENETIC AGE AND AGE ACCELERATION WERE INVERSELY ASSOCIATED WITH 6MWD; ONLY GRIMAGE WAS INVERSELY ASSOCIATED WITH PA. LONGITUDINAL CHANGE IN HANNUM-AGE WAS INVERSELY ASSOCIATED WITH CHANGE IN EC AT 12 WEEKS (N = 94). NO MEASURES OF BIOLOGICAL AGE WERE SIGNIFICANTLY ASSOCIATED WITH PROSPECTIVE AES OVER 1.3 +/- 0.3 YEARS. CONCLUSIONS: EPIGENETIC MEASURES OF BIOLOGICAL AGE ARE INDEPENDENT PREDICTORS OF EC AND PA, BUT NOT AES, AMONG INDIVIDUALS WITH COPD. 2021