Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians.
- Authors
- Ehlers, Cindy L; Lind, Penelope A; Wilhelmsen, Kirk C
- Year
- 2008
- Journal
- BMC medical genetics
- PMID
- 18433502
- DOI
- 10.1186/1471-2350-9-35
- PMCID
- PMC2386778
BACKGROUND: Variation in response to the hedonic and adverse effects of a substance is in part an inherited factor that may influence its use, abuse and dependence. The mu opioid receptor is the primary site of action for opiates and individuals with polymorphisms in this receptor appear to have variation in the CNS effects of opiates. Several studies have suggested that this receptor may also mediate some of the effects of non-opioid drugs, such as alcohol. The purpose of this study was to investigate associations between 13 single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) with self-reported responses to alcohol, an endophenotype associated with the development of alcohol dependence, in American Indians living on eight contiguous reservations. METHODS: Each participant gave a blood sample and completed a structured diagnostic interview. Additionally, response to alcohol was indexed using the expectation version of the subjective high assessment scale (SHAS-E). SNPs were genotyped in 251 participants and data analyses were conducted using SOLAR. RESULTS: The estimated heritability (h2) for the SHAS-E phenotypes ranged from 0.01 to 0.28. Endorsing the expectation of a more intense response on one or more of the following items from the SHAS-E: buzzed, clumsy, dizzy, drunk, effects, high, nausea, sleepy, talkative, terrible, and/or uncomfortable after imbibing 2-3 drinks was significantly associated with having at least one minor allele for at least one of 7 SNPs (p < 0.01) in the OPRM1 receptor gene. CONCLUSION: These studies provide data to suggest that the minor allele, for most of the polymorphisms in the OPRM1 receptor gene investigated, was found to be associated with a more intense, and/or more adverse, response to alcohol, traits that are significantly correlated with lowered quantity of alcohol consumption and less susceptibility to dependence in this Indian population. These data further suggest that making conclusions on the role of the mu opiod receptor gene in the development of alcohol dependence may be limited if only one polymorphism in the gene is evaluated in isolation.
A schematic representation of OPRM1 Gene Structure, Linkage. Disequilibrium and Genotyped SNPs. The gene structure of OPRM1 is shown with exons numbered from 1 to 4 and relative exon size denoted by the width of the vertical bars. Thirteen SNPs analyzed in this study are shown in relation to their location across OPRM1. Linkage disequilibrium (LD; shown below the gene structure) data, as measured by the correlation coefficient r2 statistic, was generated using Haploview [81]. LD causes tightly linked genetic variants to be highly correlated. Shading represents correlation magnitudes between low r2 (white) and high r2 (red).
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