Cargando…

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

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 var...

Descripción completa

Detalles Bibliográficos
Autores principales: Ehlers, Cindy L, Lind, Penelope A, Wilhelmsen, Kirk C
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386778/
https://www.ncbi.nlm.nih.gov/pubmed/18433502
http://dx.doi.org/10.1186/1471-2350-9-35
_version_ 1782155260513484800
author Ehlers, Cindy L
Lind, Penelope A
Wilhelmsen, Kirk C
author_facet Ehlers, Cindy L
Lind, Penelope A
Wilhelmsen, Kirk C
author_sort Ehlers, Cindy L
collection PubMed
description 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 (h(2)) 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.
format Text
id pubmed-2386778
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-23867782008-05-17 Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians Ehlers, Cindy L Lind, Penelope A Wilhelmsen, Kirk C BMC Med Genet Research Article 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 (h(2)) 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. BioMed Central 2008-04-23 /pmc/articles/PMC2386778/ /pubmed/18433502 http://dx.doi.org/10.1186/1471-2350-9-35 Text en Copyright © 2008 Ehlers et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ehlers, Cindy L
Lind, Penelope A
Wilhelmsen, Kirk C
Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
title Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
title_full Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
title_fullStr Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
title_full_unstemmed Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
title_short Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
title_sort association between single nucleotide polymorphisms in the mu opioid receptor gene (oprm1) and self-reported responses to alcohol in american indians
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386778/
https://www.ncbi.nlm.nih.gov/pubmed/18433502
http://dx.doi.org/10.1186/1471-2350-9-35
work_keys_str_mv AT ehlerscindyl associationbetweensinglenucleotidepolymorphismsinthemuopioidreceptorgeneoprm1andselfreportedresponsestoalcoholinamericanindians
AT lindpenelopea associationbetweensinglenucleotidepolymorphismsinthemuopioidreceptorgeneoprm1andselfreportedresponsestoalcoholinamericanindians
AT wilhelmsenkirkc associationbetweensinglenucleotidepolymorphismsinthemuopioidreceptorgeneoprm1andselfreportedresponsestoalcoholinamericanindians