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Alcohol Clin Exp Res. 2017 Jun;41(6):1093-1104. doi: 10.1111/acer.13384. Epub 2017 Apr 26.

Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers.

Author information

1
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
3
Department of Mental Health, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.

Abstract

BACKGROUND:

The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers.

METHODS:

Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol contents (0.03 to 0.1%). DNA was analyzed for OPRM1 AA versus AG/GG (*G) genotypes, DAT1 10-repeat allele (A10) versus 9 or lesser alleles (A9), and ancestral informative markers.

RESULTS:

There were significant epistatic interactions between OPRM1 and DAT1 genotypes. Subjective High Assessment Scale scores after alcohol consumption were highest in *G and A9 carriers, and lowest in *G and A10 carriers. Negative subjective effects were also highest in *G and A9 carriers. Effects were similar in a sensitivity analysis limited to Caucasian subjects. There were independent and epistatic interactions on drinking. The OPRM1 *G allele was independently associated with fewer heavy drinking days. The A9 allele was associated with a greater number of drinking days, which was attenuated in carriers of the *G allele.

CONCLUSIONS:

These findings highlight the biological importance of interactions between these 2 genes and interactions between brain opioid and dopamine systems.

KEYWORDS:

A118G; Alcohol; Dopamine Transporter Gene; Intermediate Phenotype; Mu Opioid Receptor Gene; Polymorphism

PMID:
28376280
PMCID:
PMC5483245
DOI:
10.1111/acer.13384
[Indexed for MEDLINE]
Free PMC Article

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