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儿茶酚-O-甲基转移酶Val158Met基因多态性与大麻依赖易感性

The catechol-O-methyl transferase Val158Met polymorphism and susceptibility to cannabis dependence.

作者信息

Baransel Isir Aysun Baransel, Oguzkan Sibel, Nacak Muradiye, Gorucu Senay, Dulger Hikmet Ergin, Arslan Ahmet

机构信息

Department of Forensic Medicine, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.

出版信息

Am J Forensic Med Pathol. 2008 Dec;29(4):320-2. doi: 10.1097/PAF.0b013e3181847e56.

DOI:10.1097/PAF.0b013e3181847e56
PMID:19259017
Abstract

Cannabis stimulates dopamine release and activates dopaminergic reward neurons in central pathways that lead to enhanced dependence. Catechol-O-methyl transferase (COMT) inactivates amplified extraneuronally released dopamine. A functional polymorphism (COMT Val158Met) resulting in increased enzyme activity has been associated with polysubstance abuse and addiction to heroin and methamphetamine. The aim of this study was to examine the relationship between the COMT Val158Met polymorphism and use of cannabis. Fifty-five cannabis users and 75 normal controls were enrolled in this study. Polymerase chain reaction-based genotyping was used to evaluate the presence of COMT gene polymorphism. There was a difference in genotype frequencies between cannabis users and controls, including the distribution of the COMT genotypes (H/H, H/L) (P < 0.001) and alleles (H, L) (P < 0.01), when comparing the patient groups and the control individuals. However, LL genotype distribution was similar between the groups. These results suggest a significant association between COMT Val158Met polymorphism and susceptibility to cannabis dependence.

摘要

大麻会刺激多巴胺释放,并激活中枢通路中的多巴胺能奖赏神经元,从而导致成瘾性增强。儿茶酚-O-甲基转移酶(COMT)可使细胞外释放的多巴胺失活。一种导致酶活性增加的功能性多态性(COMT Val158Met)与多种物质滥用以及海洛因和甲基苯丙胺成瘾有关。本研究的目的是探讨COMT Val158Met多态性与大麻使用之间的关系。本研究纳入了55名大麻使用者和75名正常对照者。采用基于聚合酶链反应的基因分型方法来评估COMT基因多态性的存在。比较患者组和对照个体时,大麻使用者和对照者之间的基因型频率存在差异,包括COMT基因型(H/H、H/L)的分布(P < 0.001)和等位基因(H、L)的分布(P < 0.01)。然而,两组之间LL基因型分布相似。这些结果表明COMT Val158Met多态性与大麻成瘾易感性之间存在显著关联。

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