Association of OPRD1 polymorphisms with heroin dependence in a large case-control series.
Association of OPRD1 polymorphisms with heroin dependence in a large case-control series.
复制标题
OPRD1多态性与海洛因依赖性的关联在大病例对照系列中。
DOI：
10.1111/j.1369-1600.2012.00445.x
复制
发表时间：
2014-01
影响因子：
3.4
通讯作者：
Montgomery GW
中科院分区：
文献类型：
--
作者：
Nelson EC;Lynskey MT;Heath AC;Wray N;Agrawal A;Shand FL;Henders AK;Wallace L;Todorov AA;Schrage AJ;Madden PA;Degenhardt L;Martin NG;Montgomery GW
编码阿片受体（OPRM 1，OPRD 1和OPRK 1）的基因是参与海洛因依赖风险的明显候选者。先前的关联研究通常具有中等大小的样本，包括这些基因的有限的单核苷酸多态性（SNP）覆盖，并且产生不一致的结果。目前调查的参与者包括从澳大利亚新南威尔士州的维持诊所确定的1459例海洛因依赖病例，以及从澳大利亚双胞胎和兄弟姐妹样本中选择的1495名不符合DSM-IV终生酒精或非法药物依赖标准的无关个体（非依赖性控制），和531控制确定的经济困难的社区附近的维护诊所。在该样本中，共对136个OPRM 1、OPRD 1和OPRK 1 SNP进行了基因分型。在用主成分分析控制混合物后，我们将病例与非依赖性对照进行比较，发现4个OPRD 1 SNP处于相当高的连锁不平衡中，调整后的p值仍然显著（例如，rs 2236857; OR 1.25; p=2.95 × 10−4）复制了先前报道的关联。事后分析显示，OPRD 1中的两个SNP（rs 2236857和rs 581111）GA单倍型与更高的风险相关（OR 1.68; p=1.41 × 10−5）。没有OPRM 1或OPRK 1 SNP达到超过标称显著性。病例与邻近对照组的比较仅达到名义上的显著性。我们的研究结果重复了先前的报告，提供了强有力的证据，暗示OPRD 1 SNP，特别是两个SNP（rs 2236857和rs 581111）GA单倍型在海洛因依赖的责任。没有发现支持涉及OPRM 1或OPRK 1 SNP的类似关联。
Genes encoding the opioid receptors (OPRM1, OPRD1, and OPRK1) are obvious candidates for involvement in risk for heroin dependence. Prior association studies commonly had samples of modest size, included limited single nucleotide polymorphism (SNP) coverage of these genes, and yielded inconsistent results. Participants for the current investigation included 1459 heroin dependent cases ascertained from maintenance clinics in New South Wales, Australia, 1495 unrelated individuals selected from an Australian sample of twins and siblings as not meeting DSM-IV criteria for lifetime alcohol or illicit drug dependence (non-dependent controls), and 531 controls ascertained from economically-disadvantaged neighborhoods in proximity to the maintenance clinics. A total of 136 OPRM1, OPRD1, and OPRK1 SNPs were genotyped in this sample. After controlling for admixture with principal components analysis, our comparison of cases to non-dependent controls found 4 OPRD1 SNPs in fairly high linkage disequilibrium for which adjusted p values remained significant (e.g., rs2236857; OR 1.25; p=2.95 × 10−4) replicating a previously reported association. A post-hoc analysis revealed that the two-SNP (rs2236857 and rs581111) GA haplotype in OPRD1 is associated with greater risk (OR 1.68; p=1.41 × 10−5). No OPRM1 or OPRK1 SNPs reached more than nominal significance. Comparisons of cases to neighborhood controls reached only nominal significance. Our results replicate a prior report providing strong evidence implicating OPRD1 SNPs and, in particular, the two SNP (rs2236857 and rs581111) GA haplotype in liability for heroin dependence. Support was not found for similar association involving either OPRM1 or OPRK1 SNPs.
登录
查看更多内容
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
--
作者：
Merikangas, KR;Stolar, M;Rounsaville, BJ
通讯作者：
Rounsaville, BJ
影响因子：
4.2
作者：
Glatt, Stephen J.;Bousman, Chad;Tsuang, Ming T.
通讯作者：
Tsuang, Ming T.
影响因子：
--
作者：
Mahajan, Supriya D.;Aalinkeel, Ravikumar;Reynolds, Jessica L.;Nair, Bindukumar B.;Sykes, Donald E.;Hu, Zihua;Bonaiu, Adela;Ding, Hong;Prasad, Paras N.;Schwartz, Stanley A.
通讯作者：
Schwartz, Stanley A.
影响因子：
3.8
作者：
Li, J;Ji, L
通讯作者：
Ji, L