A Polymorphism of the ??-Opioid Receptor Gene (OPRM1) and Sensitivity to the Effects of Alcohol in Humans

University of Colorado, Boulder, CO 80309-0345, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 01/2005; 28(12):1789-95. DOI: 10.1097/01.ALC.0000148114.34000.B9
Source: PubMed


Recent research has implicated the endogenous opioid system in the development of alcohol use disorders. The A118G polymorphism of the OPRM1 gene has been shown to confer functional differences to mu-opioid receptors, such that the G variant binds beta-endorphin three times more strongly than the A variant. The goal of this study was to test whether the A118G polymorphism is associated with sensitivity to the effects of alcohol.
Participants who were either homozygous for the A allele (n = 23) or heterozygous (n = 15) received intravenous doses of alcohol designed to reach three target levels of breath alcohol concentration: 0.02, 0.04, and 0.06. The testing procedure consisted of measures of subjective intoxication, stimulation, sedation, and mood states at baseline and at each of the three target breath alcohol concentrations.
The results suggested that individuals with the G allele reported higher subjective feelings of intoxication, stimulation, sedation, and happiness across trials as compared with participants with the A allele. Furthermore, participants with the G allele were almost three times more likely to report a positive family history of alcohol use disorders than participants with the A allele.
These findings may help to explain previous research suggesting that naltrexone is more effective among individuals with the G allele. A medication that reduces feelings of euphoria after alcohol consumption may be more successful among individuals with a genetic predisposition to greater feelings of euphoria after consuming alcohol.

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    • "The OPRM1 gene encodes for the µ-opioid receptor (MOR, receptor of endogenous opioids including heroin, morphine, and methadone). The OPRM1 polymorphism consists of an adenine to guanine substitution which affects the reinforcing (thus addictive) effect of drugs in various brain regions ( Ray et al., 2011) This polymorphism has been linked to a variety of substance use characteristics including sensitivity to the effects of alcohol (Ray & Hutchison, 2004) and adolescent alcohol misuse (Miranda et al., 2010), heroin addiction (Shi et al., 2002), and nicotine reinforcement ( Ray et al., 2006). OPRM1 has also been associated with neural sensitivity to social rejection (Way, Taylor, & Eisenberger, 2009). "

    Handbook of biosocial criminology, Edited by Matt DeLisi, Matthew G. Vaughn, 01/2015: pages 101-114; Routledge.
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    • "An experimental study focusing on behavioral mechanisms of alcohol reward in a sample of heavy drinkers has shown that compared with A-allele homozygotes, G-allele carriers report greater subjective reinforcement from alcohol in the laboratory (Ray and Hutchison, 2004). Similar results were obtained in a naturalistic study of the effects of alcohol (Ray et al., 2010b). "
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    ABSTRACT: Subjective response to alcohol represents a marker of alcoholism risk. The A118G single-nucleotide polymorphism (SNP) of the mu opioid receptor (OPRM1) gene has been associated with subjective response to alcohol. Recently, the dopamine transporter (DAT1) variable number of tandem repeat (VNTR; SLC6A3) has been found to interact with the OPRM1 A118G SNP in predicting neural and behavioral responses to naltrexone and to alcohol. This exploratory study examines the OPRM1 × DAT1 interaction on subjective responses to alcohol. Non-treatment-seeking problem drinkers (n = 295) were assessed in the laboratory for alcohol dependence. Following prospective genotyping for the OPRM1 gene, 43 alcohol-dependent individuals were randomized to two intravenous infusion sessions, one of alcohol (target BrAC = 0.06 g/dl) and one of saline. Measures of subjective responses to alcohol were administered in both infusion sessions. Analyses revealed significant Alcohol × OPRM1 × DAT1 interactions for alcohol-induced stimulation, vigor and positive mood as well as significant Alcohol × OPRM1 × DAT1 × Time interactions for stimulation and positive mood. These effects were such that, compared with other genotype groups, OPRM1 G-allele carriers + DAT1 A10 homozygotes reported steeper increases in stimulation and positive mood across rising BrAC, when compared with placebo. All Alcohol × OPRM1 × DAT1 interactions remained significant when analyses were restricted to a subsample of Caucasian participants (n = 34); however, 4-way interactions did not reach statistical significance in this subsample. This study suggests that the contribution of OPRM1 genotype to alcohol-induced stimulation, vigor and positive mood is moderated by DAT1 genotype. These findings are consistent with the purported interaction between opioidergic and dopaminergic systems in determining the reinforcing properties of alcohol.
    Alcohol and Alcoholism 01/2014; 49(3). DOI:10.1093/alcalc/agt183 · 2.89 Impact Factor
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    • "Human genetic studies have identified polymorphisms associated with alcohol dependence in genes that comprise various neurotransmitter signaling pathways, including dopaminergic (e.g., MAOA, COMT, and DRD2, ANKK1, TTC12 and NCAM1; Kohnke et al. 2005; Yang et al. 2008; Tikkanen et al. 2009; Hendershot et al. 2011); serotonergic (e.g., 5-HTT, SLC6A4 and HTR3A, HTR3B, HTR1B; van der Zwaluw et al. 2010; Cao et al. 2013; Seneviratne et al. 2013); GABAergic (e.g., GABRA1, GABRA2 and GABRG1; Agrawal et al. 2006; Dick and Bierut 2006; Enoch 2008), glutamatergic (GRM8; Chen et al. 2009), and cholinergic systems (e.g., CHRM2 and CHRNA5, CHRNB2; Luo et al. 2005; Ehringer et al. 2007; Wang et al. 2009); opioid receptors (e.g., prodynorphin; PDYN; Flory et al. 2011, OPRM1, OPRD1 and OPRK1; Ray and Hutchison 2004; Zhang et al. 2008; Ashenhurst et al. 2012), and tachykinin receptor 3 (TACR3; Foroud et al. 2008). "
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    ABSTRACT: Alcohol abuse and alcoholism incur a heavy socioeconomic cost in many countries. Both genetic and environmental factors contribute to variation in the inebriating effects of alcohol and alcohol addiction among individuals within and across populations. From a genetics perspective, alcohol sensitivity is a quantitative trait determined by the cumulative effects of multiple segregating genes and their interactions with the environment. This review summarizes insights from model organisms as well as human populations that represent our current understanding of the genetic and genomic underpinnings that govern alcohol metabolism and the sedative and addictive effects of alcohol on the nervous system. Electronic supplementary material The online version of this article (doi:10.1007/s00438-013-0808-y) contains supplementary material, which is available to authorized users.
    MGG Molecular & General Genetics 01/2014; 289(3). DOI:10.1007/s00438-013-0808-y · 2.73 Impact Factor
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