Citation

Bendre M, Comasco E, Checknita D, Tiihonen J, Hodgins S, Nilsson KW. Alcohol Clin. Exp. Res. 2018; 42(3): 508-519.

Affiliation

Centre for Clinical Research, Uppsala University, County Hospital, Västerås, Sweden.

Copyright

(Copyright © 2018, John Wiley and Sons)

DOI

10.1111/acer.13578

PMID

29222910

Abstract

BACKGROUND: Epigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the Monoamine Oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on fifty-three young adult males and aimed to determine: whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment; and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment.

METHODS: MAOA-uVNTR genotypes with ≤ 3 and > 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorder Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman's method, respectively.

RESULTS: Carriers of the S allele who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score, in contrast to L allele carriers. Carriers of the S allele who reported higher AUDIT-C score, and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L allele carriers.

CONCLUSION: Intronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Language: en

Keywords

MAOA- uVNTR; Alcohol; DNA methylation; Maltreatment; gene by environment