Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians Public Deposited

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Creator
  • Lind, Penelope A
    • Other Affiliation: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia
  • Ehlers, Cindy L
    • Other Affiliation: Department of Molecular and Experimental Medicine, Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA, USA
  • Wilhelmsen, Kirk
    • Affiliation: School of Medicine, Department of Genetics, Carolina Center for Genome Sciences, Department of Neurology, Bowles Center for Alcohol Studies
Abstract
  • Abstract 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.
Date of publication
Identifier
  • doi:10.1186/1471-2350-9-35
  • 18433502
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Cindy L Ehlers et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Medical Genetics
Journal volume
  • 9
Journal issue
  • 1
Page start
  • 35
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2350
Bibliographic citation
  • BMC Medical Genetics. 2008 Apr 23;9(1):35
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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