Evaluation of OPRM1 variants in heroin dependence by family-based association testing and meta-analysis
Evaluation of OPRM1 variants in heroin dependence by family-based association testing and meta-analysis
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DOI：
10.1016/j.drugalcdep.2007.02.022
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发表时间：
2007-10-08
影响因子：
4.2
通讯作者：
Tsuang, Ming T.
中科院分区：
文献类型：
--
作者：
Glatt, Stephen J.;Bousman, Chad;Tsuang, Ming T.
OPRM 1编码μ-阿片受体，是阿片类药物依赖最常研究的候选基因。尽管有许多等位基因关联研究，但关于OPRM 1多态性在确定阿片类药物依赖风险中的作用尚未得出明确的结论。我们试图通过进行一项以家庭为基础的关联研究和荟萃分析来解决这个问题，这可能比传统的病例对照分析更可靠和更强大。首先，我们在来自473个汉族家庭的1208个个体中对OPRM 1的三个单核苷酸多态性（SNPs）进行基因分型，这些家庭是根据有两个或两个以上的兄弟姐妹患有DSM-IV定义的阿片类药物依赖而确定的。检测到Val 6Ala和Arg 111 His SNP，但具有低的次要等位基因频率（分别为0.002和0.001）。Asn 40 Asp SNP的信息量更大（次要等位基因频率：0.419），但没有观察到该多态性对阿片类药物依赖风险的显性（p = 0.810）或累加（p = 0.406）效应的显著证据。此外，对阿片类药物依赖的病例对照研究进行了荟萃分析，发现与Asn 40 Asp SNP相关的证据也同样缺乏（p = 0.859）。虽然OPRM 1多态性在阿片类药物依赖风险中的作用不能完全排除，但Asn 40 Asp多态性的主要贡献似乎不太可能。需要对特定祖先群体的样本进行进一步分析。此外，至关重要的是，测试其他OPRM 1变体（包括所有单倍型标记和氨基酸编码SNP）是否影响阿片类药物依赖的石油风险，因为Asn 40 Asp多态性只是该基因中数百个已知突变之一。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
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 Arg 1 1 1 His 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 ill 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 oil risk for opioid dependence, since the Asn40Asp polymorphism is only one of several hundred known mutations in the gene. (C) 2007 Elsevier Ireland Ltd. All rights reserved.