A pilot examination of the genome-wide DNA methylation signatures of subjects entering and exiting short-term alcohol dependence treatment programs. Philibert Robert A,Penaluna Brandan,White Teresa,Shires Sarah,Gunter Tracy,Liesveld Jill,Erwin Cheryl,Hollenbeck Nancy,Osborn Terry Epigenetics Alcoholism has a profound impact on millions of people throughout the world. However, the ability to determine if a patient needs treatment is hindered by reliance on self-reporting and the clinician's capability to monitor the patient's response to treatment is challenged by the lack of reliable biomarkers. Using a genome-wide approach, we have previously shown that chronic alcohol use is associated with methylation changes in DNA from human cell lines. In this pilot study, we now examine DNA methylation in peripheral mononuclear cell DNA gathered from subjects as they enter and leave short-term alcohol treatment. When compared with abstinent controls, subjects with heavy alcohol use show widespread changes in DNA methylation that have a tendency to reverse with abstinence. Pathway analysis demonstrates that these changes map to gene networks involved in apoptosis. There is no significant overlap of the alcohol signature with the methylation signature previously derived for smoking. We conclude that DNA methylation may have future clinical utility in assessing acute alcohol use status and monitoring treatment response. 10.4161/epi.32252

Genetic association of FKBP5 with trait resilience in Korean male patients with alcohol use disorder. Park Chun Il,Kim Hae Won,Hwang Syung Shick,Kang Jee In,Kim Se Joo Scientific reports The FKBP5 gene is known to have an important role in alcohol use disorder (AUD) in response to stress and has been reported to affect stress responses by interacting with childhood trauma. This study investigated the effects of the FKBP5 polymorphism rs1360780 and childhood trauma on trait resilience in male patients with AUD. In addition, allele-specific associations between FKBP5 DNA methylation and resilience were examined. In total, 297 men with AUD were assessed for alcohol use severity, childhood trauma, resilience, and impulsivity. Genotyping for FKBP5 rs1360780 and DNA methylation were analyzed. The effects of the rs1360780 single nucleotide polymorphism (SNP) and clinical variables on resilience were tested using linear regression analysis. Possible associations between FKBP5 DNA methylation and resilience were tested with partial correlation analysis. The rs1360780 risk allele, a low education level, and high impulsivity were associated with diminished resilience, whereas no significant main or interaction effect of childhood trauma with the SNP rs1360780 genotype on resilience was shown. No significant association between FKBP5 DNA methylation and resilience was found. The present study demonstrated the involvement of the rs1360780 risk allele in trait resilience in men with AUD, suggesting that the genetic vulnerability of FKBP5 may influence resilience related to AUD. 10.1038/s41598-021-98032-6

N-methyl-D-aspartate 2b receptor subtype (NR2B) promoter methylation in patients during alcohol withdrawal. Biermann Teresa,Reulbach Udo,Lenz Bernd,Frieling Helge,Muschler Marc,Hillemacher Thomas,Kornhuber Johannes,Bleich Stefan Journal of neural transmission (Vienna, Austria : 1996) NMDA receptors and especially the NR2B receptor subtype play a crucial role during chronic ethanol consumption and alcohol withdrawal. Therefore, the NR2B receptor subtype expression in peripheral blood cells of 32 male patients suffering from alcohol dependency were assessed through quantitative RT-PCR and to explore regulating epigenetic mechanisms, a methylation analysis was conducted using bisulfite sequencing of a fragment of the NR2B promoter region. The expression of the NR2B receptor increased significantly during the first 24 h of withdrawal treatment (day 1; t = 4.1, P = 0.001), and also on and day 3 (t = 2.4; P = 0.029). The severity of alcohol drinking pattern, measured by lifetime drinking and daily ethanol intake, was negatively correlated with the methylation of a defined cluster of five CPG-sites within the NR2B promoter (lifetime drinking: Spearman's rho = -0.55; P = 0.013; daily ethanol intake: rho = -0.46; P = 0.043). These findings might explain the observation of an impact of alcohol consumption patterns on the gravity of withdrawal symptoms. 10.1007/s00702-009-0212-2

Hypermethylation of OPRM1 promoter region in European Americans with alcohol dependence. Zhang Huiping,Herman Aryeh I,Kranzler Henry R,Anton Raymond F,Simen Arthur A,Gelernter Joel Journal of human genetics The μ-opioid receptor mediates rewarding effects of alcohol and illicit drugs. We hypothesized that altered DNA methylation in the μ-opioid receptor gene (OPRM1) might influence the vulnerability to alcohol dependence (AD). Genomic DNA was extracted from the peripheral blood of 125 European Americans with AD and 69 screened European American controls. Methylation levels of 16 CpGs in the OPRM1 promoter region were examined by bisulfite sequencing analysis. A multivariate analysis of covariance was conducted to analyze AD-associated methylation changes in the OPRM1 promoter region, using days of intoxication in the past 30 days, sex, age, ancestry proportion and childhood adversity (CA) as covariates. Three CpGs (80, 71, and 10 bp upstream of the OPRM1 translation start site) were more highly methylated in AD cases than in controls (CpG-80: P=0.033; CpG-71: P=0.004; CpG-10: P=0.008). Although these sites were not significant after correction for multiple comparisons, the overall methylation level of the 16 CpGs was significantly higher in AD cases (13.6%) than in controls (10.6%) (P=0.049). Sex and CA did not significantly influence OPRM1 promoter methylation levels. Our findings suggest that OPRM1 promoter hypermethylation may increase the risk for AD and other substance dependence disorders. 10.1038/jhg.2012.98