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Evaluation of OPRM1 variants in heroin dependence by family-based association testing and meta-analysis.

Abstract：

:OPRM1, which codes for the mu-opioid receptor, is the most frequently studied candidate gene for opioid dependence. Despite numerous allelic association studies, no definitive conclusion has been reached regarding the role of OPRM1 polymorphisms in determining risk for opioid dependence. We attempted to resolve this by conducting a family-based association study and meta-analysis which may be more robust and powerful, respectively, than traditional case-control analyses. First, we genotyped three single nucleotide polymorphisms (SNPs) of OPRM1 in 1208 individuals from 473 Han Chinese families ascertained on the basis of having two or more siblings with DSM-IV-defined opioid dependence. The Val6Ala and Arg111His SNPs were detected, but with low minor allele frequencies (0.002 and 0.001, respectively). The Asn40Asp SNP was more informative (minor allele frequency: 0.419), but no significant evidence was observed for either a dominant (p=0.810) or additive (p=0.406) effect of this polymorphism on risk for opioid dependence. In addition, a meta-analysis of case-control studies of opioid dependence was performed, and found a similar lack of evidence for an association with the Asn40Asp SNP (p=0.859). Although a role of OPRM1 polymorphisms in determining risk for opioid dependence cannot be entirely discounted, a major contribution of the Asn40Asp polymorphism seems unlikely. Further analysis is warranted in samples from specific ancestral groups. In addition, it is critical that other OPRM1 variants, including all haplotype-tagging and amino-acid-coding SNPs, be tested for an influence on risk for opioid dependence, since the Asn40Asp polymorphism is only one of several hundred known mutations in the gene.

journal_name

Drug Alcohol Depend

journal_title

Drug and alcohol dependence

authors

Glatt SJ,Bousman C,Wang RS,Murthy KK,Rana BK,Lasky-Su JA,Zhu SC,Zhang R,Li J,Zhang B,Li J,Lyons MJ,Faraone SV,Tsuang MT

doi

10.1016/j.drugalcdep.2007.02.022

subject

Has Abstract

pub_date

2007-10-08 00:00:00

pages

159-65

issue

2-3

eissn

0376-8716

issn

1879-0046

pii

S0376-8716(07)00103-2

journal_volume

90

pub_type

杂志文章,meta分析

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