The OPRM1 A118G polymorphism: converging evidence against associations with alcohol sensitivity and consumption

Abstract

The endogenous opioid system may be involved in the development and maintenance of alcohol use disorder (AUD) and is a target for existing AUD pharmacotherapies. A functional polymorphism of the mu-opioid receptor gene (OPRM1 A118G, rs1799971) may alter the risk of developing AUD. Human laboratory studies have demonstrated that minor allele carriers self-administer more alcohol, show greater sensitivity to alcohol's effects, and exhibit increased alcohol-induced dopamine release. On the other hand, large genome-wide association studies and meta-analyses of candidate gene studies have not found an association between this genotype and alcohol dependence diagnosis. Given this discrepancy, the present study sought to verify whether OPRM1 A118G was associated with alcohol self-administration, subjective response to alcohol, and craving in a sample of 106 social drinkers of European ancestry who completed an intravenous alcohol self-administration session. We found no relationship between OPRM1 rs1799971 genotype and subjective response to alcohol or craving. OPRM1 genotype was not associated with total alcohol exposure or likelihood of attaining a binge-level exposure (80 mg%) during the intravenous alcohol self-administration session. Analysis of 90-day Timeline Followback interview data in a larger sample of 965 participants of European ancestry found no relationship between OPRM1 genotype and alcohol consumption in either alcohol dependent or non-dependent participants. These findings suggest that there may not be an association between OPRM1 rs1799971 genotype and alcohol consumption or sensitivity in individuals of European ancestry.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1

OPRM1 genotype and alcohol-induced subjective response in the intravenous alcohol self-administration sample. Following the administration of a priming dose of alcohol, subjects reported how intoxicated they felt (“Feel Intoxicated”) and how much they liked the effects of alcohol (“Like Effects”). The horizontal line in the middle of each box indicates the median, while the bottom and top borders of the box represent the 25th and 75th percentile values, respectively. No significant differences were observed between genotype groups

Fig. 2

Kaplan-Meier survival curves examining the effect of OPRM1 genotype on rate of binging in the intravenous alcohol self-administration sample. Panels show the cumulative probability of achieving a binge-level exposure (estimated blood alcohol concentration of 80 mg%) during the intravenous alcohol self-administration session in males and females. There were no significant differences between genotype groups

Fig. 3

OPRM1 genotype and binge drinking days in the alcohol use disorder assessment sample. Histograms depict the distribution of binge drinking days in participants without a lifetime history of alcohol dependence (a) and with a lifetime history of alcohol dependence (b). The distributions were not significantly different between genotype groups