Human kappa opioid receptor gene (OPRK1) polymorphism is associated with opiate addiction
Human kappa opioid receptor gene (OPRK1) polymorphism is associated with opiate addiction
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DOI：
10.1002/ajmg.b.30510
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发表时间：
2007-09-05
影响因子：
2.8
通讯作者：
Donnini, C.
中科院分区：
文献类型：
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作者：
Gerra, G.;Leonardi, C.;Donnini, C.
阿片受体的变种是成瘾的明显候选者。Kappa阿片受体(KOR)系统似乎在应激反应、阿片类药物戒断和对精神兴奋剂的反应中发挥作用，从而抑制中脑边缘多巴胺。据报道，KOR基因多态与实验动物自愿饮酒行为的易感性有关。在人类中，最近发现的KOR基因的36G>；T单核苷酸多态(SNP)与物质依赖有关，但尚无定论。在本研究中，对106名海洛因成瘾者(西欧、高加索人)和70名种族和性别匹配、无物质使用障碍病史的健康对照组进行了基因分型。海洛因依赖者KOR36G>；T SNP频率显著高于对照组(Fisher‘s Exact=0.044；Pearson chi(2)=4.2734，P=0.039；似然比chi(2)检验4.6156，P=0.032)。尽管KOR沉默的多态性可能对mRNA转录没有明显的影响，但转录后的机制，如mRNA的稳定性、翻译效率和可调性可能会损害kappa受体系统的功能，增加物质使用障碍的风险。具体地说，u-kappa阿片类药物失衡引起的神经生物学变化可能是脆弱的人格特征和危险行为的基础。(C)2007年Wiley-Liss，Inc.
Variants of the opioid receptors are the obvious candidates underlying addiction. The kappa opioid receptor (KOR) system seems to play a role in stress responsivity, opiate withdrawal and responses to psycho-stimulants, inhibiting mesolimbic dopamine. KOR gene polymorphisms have been reported to contribute to predisposition to voluntary alcohol-drinking behavior in experimental animals. In humans, the 36G > T single nucleotide polymorphism (SNP) on KOR gene, that was recently identified, has been found associate with substance dependence, with inconclusive findings. In the present study, 106 heroin addicts (West European, Caucasians) and 70 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. The frequency of KOR 36G > T SNP was significantly higher among heroin-dependent individuals compared with control subjects (Fisher's exact = 0.044; Pearson chi(2) =4.2734, P=0.039; likelihood ratio chi(2) tests 4.6156, P=0.032). Although KOR silent polymorphisms may apparently have no consequences on mRNA transcription, post-transcriptional mechanisms, such as mRNA stability, translation efficiency, and regulability may impair the function of kappa receptors system, with increased risk for substance use disorders. In specific, the neurobiological changes induced by mu-kappa opioid imbalance could underlie vulnerable personality traits and risk behavior. (c) 2007 Wiley-Liss, Inc.