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

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Authors: Weerts, Elise M; Wand, Gary S; Maher, Brion; Xu, Xiaoqiang; Stephens, Mary Ann; Yang, Xiaoju; McCaul, Mary E
Year: 2017
Journal: Alcoholism, clinical and experimental research
PMID: 28376280
DOI: 10.1111/acer.13384
PMCID: PMC5483245

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.

Figure 1

Breath Alcohol Content (BAC) during the cumulative alcohol dosing procedure. Data are mean +SEM BAC for each genotype subgroup as determined at baseline, 15 min after consumption of each drink, and at 45-minute intervals for the remainder of the session. The x-axis is the time line for the session, and administration times of the placebo drink (P) and each active alcohol drink (A1, A2, A3) are indicated with arrows. Data points are slightly displaced on the x-axis for visual clarity.

Figure 2

Mean total SHAS scores reported at each time point during the cumulative alcohol dosing procedure. The x-axis is the time line for the session, and administration times of the placebo drink (P) and each active alcohol drink (A1, A2, A3) are indicated with arrows. Data are adjusted means (SEM) for each of the genotype subgroups. Means were adjusted for sex, AIMs and number of drinking days.

Figure 3

Mean DEQ VAS negative scores reported at each time point during the cumulative alcohol dosing procedure. Other details as in Figure 2.

Figure 4

Mean total scores for A. stimulation and B. sedation subscales of the Biphasic Alcohol Effects Scale (BAES), C. positive effects on the Drug Effects Questionairre Visual Analog Scale (DEQ VAS), and D. the Tension and Anxiety subscale of the Profile of Mood States scale (POMS T&A) as reported at each time point during the cumulative alcohol dosing procedure. Other details as in Figure 2.

#	Section	Preview
40	Discussion	To date, the evidence for a role of the OPRM1 A118 SNP in AUD risk has been mixed, with different…
41	Discussion	Clinical and preclinical data provide strong evidence that the rewarding and aversive effects of…
42	Discussion	2011, Weerts et al., 2013) and greater dopamine release in response to alcohol (Ramchandani et al.,…
43	Discussion	The current study has a number of strengths, which help validate the findings and add to the growing…
44	Discussion	reduce the impact of nicotine use and dependence. Both the OPRM1 A118G SNP and DAT1 VTNR…
45	Discussion	We acknowledge there are limitations in the study. First, while sample size is relatively large for…
46	Discussion	out of many does not account for the influence of other genes that affect alcohol sensitivity and…
47	Discussion	blinding of the placebo drink, controlled dosing and BAC achieved, drinks are less palatable than an…
48	Discussion	The current study provides support for the influence of the interactive effects of DAT1 and OPRM1…

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