Department of Clinical Neurosciences, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India.
Centre for Addiction Medicine, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India.
Am J Med Genet B Neuropsychiatr Genet. 2021 Apr;186(3):183-192. doi: 10.1002/ajmg.b.32833. Epub 2021 Jan 25.
Treatment strategies for alcohol use disorder (AUD) aim for abstinence or harm reduction. While deranged biochemical parameters reverse with alcohol abstinence, whether molecular changes at the epigenetic level reverse is not clearly understood. We investigated whether the reduction from high alcohol use reflects DNA methylation at the gene-specific and global level. In subjects seeking treatment for severe AUD, we assessed gene-specific (aldehyde dehydrogenase [ALDH2]/methylene tetrahydrofolate reductase [MTHFR]) and global (long interspersed elements [LINE-1]) methylation across three-time points (baseline, after detoxification and at an early remission period of 3 months), in peripheral blood leukocytes. We observed that both gene-specific and global DNA methylation did not change over time, irrespective of the drinking status at 3 months (52% abstained from alcohol). Further, we also compared DNA methylation in AUD subjects with healthy controls. At baseline, there was a significantly higher gene-specific DNA methylation (ALDH2: p < .001 and MTHFR: p = .001) and a significant lower global methylation (LINE-1: p = .014) in AUD as compared to controls. Our results suggest that epigenetic changes at the DNA methylation level associated with severe AUD persist for at least 3 months of treatment.
治疗酒精使用障碍（AUD）的策略旨在戒酒或减少伤害。虽然紊乱的生化参数随着戒酒而逆转，但在表观遗传水平上的分子变化是否逆转尚不清楚。我们研究了从高饮酒量减少是否反映了基因特异性和全基因组水平的 DNA 甲基化。在寻求严重 AUD 治疗的受试者中，我们评估了外周血白细胞中三个时间点（基线、解毒后和 3 个月的早期缓解期）的基因特异性（乙醛脱氢酶[ALDH2]/亚甲基四氢叶酸还原酶[MTHFR]）和全基因组（长散布元件[LINE-1]）甲基化。我们观察到，无论 3 个月时的饮酒状态如何（52%的人戒酒），基因特异性和全基因组 DNA 甲基化都不会随时间变化。此外，我们还比较了 AUD 受试者和健康对照组的 DNA 甲基化。在基线时，AUD 组的基因特异性 DNA 甲基化（ALDH2：p<.001 和 MTHFR：p=0.001）显著升高，而全基因组甲基化（LINE-1：p=0.014）显著降低。我们的结果表明，与严重 AUD 相关的 DNA 甲基化水平的表观遗传变化在至少 3 个月的治疗中持续存在。
