Case-control association analysis of polymorphisms in the δ-opioid receptor, OPRD1, with cocaine and opioid addicted populations.
Case-control association analysis of polymorphisms in the δ-opioid receptor, OPRD1, with cocaine and opioid addicted populations.
复制标题
DOI：
10.1016/j.drugalcdep.2012.06.023
复制
发表时间：
2013-01-01
影响因子：
4.2
通讯作者：
Berrettini, W. H.
中科院分区：
文献类型：
--
作者：
Crist, R. C.;Ambrose-Lanci, L. M.;Vaswani, M.;Clarke, T. K.;Zeng, A.;Yuan, C.;Ferraro, T. N.;Hakonarson, H.;Kampman, K. M.;Dackis, C. A.;Pettinati, H. M.;O'Brien, C. P.;Oslin, D. W.;Doyle, G. A.;Lohoff, F. W.;Berrettini, W. H.
成瘾易感性和治疗反应性受遗传因素的影响很大。参与药物作用机制的基因序列变异有可能影响成瘾风险和治疗结果。阿片受体系统参与介导可卡因和阿片类药物的奖赏效应。μ-阿片受体（莫尔）传统上被认为是阿片类药物成瘾的主要靶点。然而，莫尔与许多已知的莫尔相互作用蛋白（MORIPs）相互作用并受其调节，包括δ-阿片受体（DOR）。本研究评估了编码DOR的基因OPRD 1对阿片类药物和可卡因成瘾风险的贡献。在非裔美国人（OA n=336，CA n=503）和欧洲裔美国人（OA n=1007，CA n=336）人群中分析了OPRD 1多态性与阿片类药物成瘾（OA）和可卡因成瘾（CA）的相关性。这项研究的主要发现是rs678849与非裔美国人的可卡因成瘾相关（等位基因p=0.0086）。为了复制的目的，在更大的可卡因成瘾的非裔美国人和对照人群中分析了该SNP，并证实了该关联（等位基因p=4.53×10−5; n=993）。通过对扩展人群进行荟萃分析，相关性的统计学证据大幅增加（等位基因p=8.5 × 10 −7）（p值未经FDR校正）。本研究表明，OPRD 1的多态性与非裔美国人人群的可卡因成瘾有关，并为OPRD 1变异体在药物依赖中的广泛作用提供了额外的支持。
Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The µ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR). The present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n=336, CA n=503) and European American (OA n=1007, CA n=336) populations. The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p=0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p=4.53×10−5; n=993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p=8.5 × 10 −7) (p-values non-FDR corrected). The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence.
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影响因子：
64.8
作者：
Konig, M;Zimmer, AM;Zimmer, A
通讯作者：
Zimmer, A
DOI：
10.1002/ajmg.b.30701
发表时间：
2008-10-05
期刊：
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
影响因子：
--
作者：
Luo X;Zuo L;Kranzler H;Zhang H;Wang S;Gelernter J
通讯作者：
Gelernter J
影响因子：
10.5
作者：
Kendler, KS;Prescott, CA
通讯作者：
Prescott, CA
影响因子：
64.8
作者：
Matthes, HWD;Maldonado, R;Kieffer, BL
通讯作者：
Kieffer, BL
DOI：
10.1111/j.1530-0277.2007.00339.x
发表时间：
2007-04-01
影响因子：
3.2
作者：
Gelernter, Joel;Gueorguieva, Ralitza;Krystal, John H.
通讯作者：
Krystal, John H.