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Changes in DNA methylation persist over time in males with severe alcohol use disorder—A longitudinal follow‐up study
Author(s) -
Soundararajan Soundarya,
Agrawal Arpana,
Purushottam Meera,
Anand Shravanthi Daphne,
Shankarappa Bhagyalakshmi,
Sharma Priyamvada,
Jain Sanjeev,
Murthy Pratima
Publication year - 2021
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32833
Subject(s) - dna methylation , alcohol use disorder , methylation , epigenetics , abstinence , medicine , alcohol dependence , methylenetetrahydrofolate reductase , endocrinology , alcohol , biology , genetics , gene , biochemistry , psychiatry , gene expression , genotype
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.