Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.
Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.
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阿片类药物系统基因的变异与非依赖性阿片类药物使用和海洛因依赖有关
DOI：
10.1016/j.drugalcdep.2016.08.634
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发表时间：
2016-11-01
影响因子：
4.2
通讯作者：
Kreek MJ
中科院分区：
文献类型：
--
作者：
Randesi M;van den Brink W;Levran O;Blanken P;Butelman ER;Yuferov V;da Rosa JC;Ott J;van Ree JM;Kreek MJ
海洛因成瘾是一种慢性、复发性的脑部疾病。遗传因素参与了药物成瘾的形成。这项研究的目的是确定阿片系统基因的特定变异是否与非依赖性阿片类药物使用和海洛因依赖有关。收集了四组受试者的遗传信息：非阿片依赖者(NOD)[163人]；美沙酮维持治疗(MMT)阿片依赖者(OD)[143人]；海洛因辅助治疗(HAT)阿片依赖者(MMT)耐药者(HAT)[138人]；无阿片类药物使用史的健康对照组(HC)[153人]。研究了8个阿片系统基因的82个变异体。为了确定这些基因在(A)非依赖阿片类药物使用和(B)海洛因依赖中的作用，比较了以下组：HC与NOD、HC与OD(MMT+HAT)和NOD与OD(MMT+HAT)。四个基因中的五个独特的SNP在名义上与非依赖阿片类药物使用和海洛因依赖显著相关。经多次试验校正后，增量阿片受体基因内含子SNP rs2236861与非依赖型阿片类药物使用(HC与NOD)之间的关联仍然显著(OR=0.032；预校正=0.015)。该SNP与Pnoc基因前单核苷酸多态性rs2722897存在显著的基因-基因交互作用(Hcvs.Nod)(OR=5.24；P=0.041)。这项研究发现了几个新的和一些以前报道的变异与海洛因依赖和非依赖阿片类药物使用的关联，这是一个以前没有广泛研究的重要且难以获得的组。有必要进行进一步的研究，以确认和阐明这些变种在易受非法药物使用和吸毒成瘾方面的潜在作用。
Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; pcorrected = 0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; pcorrected = 0.041) (HC vs. NOD). This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction.
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与可卡因依赖易感性相关的功能性单倍型与人脑中 PDYN 表达减少有关
DOI：
10.1038/npp.2008.187
发表时间：
2009-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
OPRD1多态性与海洛因依赖性的关联在大病例对照系列中。
影响因子：
3.4
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
通讯作者：
Montgomery GW
影响因子：
5.3
作者：
Levran O;Yuferov V;Kreek MJ
通讯作者：
Kreek MJ
影响因子：
25
作者：
Kreek, MJ;Nielsen, DA;LaForge, KS
通讯作者：
LaForge, KS
影响因子：
3.3
作者：
Clarke, S;Chen, Z;Kitchen, I
通讯作者：
Kitchen, I