TY - JOUR
T1 - Changes in DNA methylation persist over time in males with severe alcohol use disorder—A longitudinal follow-up study
AU - Soundararajan, Soundarya
AU - Agrawal, Arpana
AU - Purushottam, Meera
AU - Anand, Shravanthi Daphne
AU - Shankarappa, Bhagyalakshmi
AU - Sharma, Priyamvada
AU - Jain, Sanjeev
AU - Murthy, Pratima
N1 - Funding Information:
The authors acknowledge all the patients consented to the study. These data were presented in the Gordon Research Conference ? Alcohol and Nervous System 2018 and at NIAAA/NIH as a part of Postdoctoral Fellow recruitment in 2019 by S. S. The comments and feedback received substantially improved the manuscript. The authors sincerely acknowledge the editorial assistance of the NIH Fellows Editorial Board. S. S. received PhD Fellowship from Indian Council for Medical Research (ICMR), New Delhi, India. S. S. currently receives funding from the National Institutes of Health, as a Postdoctoral Visiting Fellow. This study was partly funded by the TVS Foundation (PI-PM) and by a grant from the Department of Science and Technology (DST), Government of India for MP on the project ?Epigenetics of Alcohol dependence.? None of the above-mentioned institutes (ICMR, NIH, TVS, DST) have a further role in study design, in the collection, analysis, or interpretation of data, in writing, and in the decision to submit the paper for publication.
Funding Information:
The authors acknowledge all the patients consented to the study. These data were presented in the Gordon Research Conference – Alcohol and Nervous System 2018 and at NIAAA/NIH as a part of Postdoctoral Fellow recruitment in 2019 by S. S. The comments and feedback received substantially improved the manuscript. The authors sincerely acknowledge the editorial assistance of the NIH Fellows Editorial Board. S. S. received PhD Fellowship from Indian Council for Medical Research (ICMR), New Delhi, India. S. S. currently receives funding from the National Institutes of Health, as a Postdoctoral Visiting Fellow. This study was partly funded by the TVS Foundation (PI‐PM) and by a grant from the Department of Science and Technology (DST), Government of India for MP on the project “Epigenetics of Alcohol dependence.” None of the above‐mentioned institutes (ICMR, NIH, TVS, DST) have a further role in study design, in the collection, analysis, or interpretation of data, in writing, and in the decision to submit the paper for publication.
Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - DNA methylation
KW - alcohol abstinence
KW - alcohol use disorder
KW - long interspersed nucleotide elements
KW - pyrosequencing
UR - http://www.scopus.com/inward/record.url?scp=85099915521&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.32833
DO - 10.1002/ajmg.b.32833
M3 - Article
C2 - 33491855
AN - SCOPUS:85099915521
VL - 186
SP - 183
EP - 192
JO - American Journal of Medical Genetics - Neuropsychiatric Genetics
JF - American Journal of Medical Genetics - Neuropsychiatric Genetics
SN - 1552-4841
IS - 3
ER -