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Changes in DNA methylation persist over time in males with severe alcohol use disorder—A longitudinal follow‐up study
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics ( IF 1.6 ) Pub Date : 2021-01-25 , DOI: 10.1002/ajmg.b.32833
Soundarya Soundararajan 1, 2, 3 , Arpana Agrawal 4 , Meera Purushottam 3, 5 , Shravanthi Daphne Anand 2 , Bhagyalakshmi Shankarappa 3 , Priyamvada Sharma 2, 6 , Sanjeev Jain 3, 5 , Pratima Murthy 2, 5
Affiliation  

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.

中文翻译:

DNA甲基化的变化在患有严重酒精使用障碍的男性中随着时间的推移持续存在——一项纵向随访研究

酒精使用障碍 (AUD) 的治疗策略旨在戒酒或减少危害。虽然精神错乱的生化参数随着戒酒而逆转,但表观遗传水平的分子变化是否逆转尚不清楚。我们调查了高酒精使用的减少是否反映了基因特异性和全局水平的 DNA 甲基化。在寻求治疗重度 AUD 的受试者中,我们评估了基因特异性(醛脱氢酶 [ ALDH2 ]/亚甲基四氢叶酸还原酶 [ MTHFR ])和全局(长散在元素 [ LINE-1]) 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)的甲基化。我们观察到,无论 3 个月时的饮酒状况如何(52% 的人戒酒),基因特异性和全局 DNA 甲基化都没有随时间变化。此外,我们还比较了 AUD 受试者与健康对照的 DNA 甲基化。在基线时,基因特异性 DNA 甲基化显着较高(ALDH2p < .001 和MTHFRp = .001)和显着较低的全局甲基化(LINE-1p= .014) 澳元与对照相比。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持续至少 3 个月的治疗。
更新日期:2021-01-25
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