Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers
Corresponding Author
Elise M. Weerts
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Reprint requests: Elise M. Weerts, PhD, Associate Professor, The Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Suite 3000, Baltimore, MD 21224; Tel.: 410-550-2781; Fax: 410-550-2780; E-mail: [email protected]Search for more papers by this authorGary S. Wand
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorBrion Maher
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Department of Mental Health, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
Search for more papers by this authorXiaoqiang Xu
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorMary Ann Stephens
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorXiaoju Yang
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorMary E. McCaul
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorCorresponding Author
Elise M. Weerts
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Reprint requests: Elise M. Weerts, PhD, Associate Professor, The Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Suite 3000, Baltimore, MD 21224; Tel.: 410-550-2781; Fax: 410-550-2780; E-mail: [email protected]Search for more papers by this authorGary S. Wand
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorBrion Maher
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Department of Mental Health, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
Search for more papers by this authorXiaoqiang Xu
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorMary Ann Stephens
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorXiaoju Yang
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorMary E. McCaul
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Search for more papers by this authorAbstract
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.
Graphical Abstract
The current study in social drinkers examine whether subjective responses to alcohol were influenced by epistatic interactions between the G-allele of OPRM1 A118G polymorphism, and a DAT1 VNTR polymorphism that results in alleles with 10 (A10) versus 9 or lesser repeats (A9). Subjective high assessment scale (SHAS) scores after alcohol consumption were highest in G and A9 carriers, and lowest in G and A10 carriers. Subjective responses in G carriers may be dependent on which DAT1 VNTR is also present.
Supporting Information
| Filename | Description |
|---|---|
| acer13384-sup-0001-FigS1.tiffTIFF image, 109 KB | Fig. S1. Distribution of self-reported race and genetic AIM components (C1 and C2) in the 127 genotyped subjects who completed the alcohol sensitivity procedure. |
| acer13384-sup-0002-FigS1Legend.docxWord document, 33.1 KB | |
| acer13384-sup-0003-AppendixS1.docxWord document, 25.3 KB | Appendix S1. Supplemental methods. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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