Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry.
Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry.
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非洲和欧洲血统受试者海洛因和可卡因成瘾的谷氨酸和 GABA 易感性位点
DOI：
10.1016/j.pnpbp.2015.08.003
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发表时间：
2016-01-04
影响因子：
5.6
通讯作者：
Kreek MJ
中科院分区：
文献类型：
--
作者：
Levran O;Peles E;Randesi M;Correa da Rosa J;Ott J;Rotrosen J;Adelson M;Kreek MJ
吸毒是一个主要的健康问题，是一种具有重要遗传成分的慢性脑部疾病。动物模型和临床研究证实谷氨酸和GABA神经传递参与药物成瘾。这项研究旨在评估这些系统中27个基因的258个变异是否会导致药物成瘾的易感性。对1860名受试者的样本进行了四项独立分析，这些受试者按滥用药物(海洛因或可卡因)和血统(非洲和欧洲)划分。在一个或两个祖先群体中，共有8个基因的11个SNP在名义上与海洛因和/或可卡因成瘾有显著关联(P<；0.01)，但经过多次测试，这些关联没有得到纠正。在这些SNP中，GAD1上游的SNP rs1978340具有潜在的功能，因为它被证明影响扣带皮质中的GABA浓度。此外，GABRB3 rs7165224；DBI rs12613135；GAD1 SNPs rs2058725、rs1978340、rs2241164和GRIN2A rs1650420已被报道与药物成瘾或相关表型有关。这项研究支持谷氨酸和GABA能系统的遗传变异与药物成瘾有关，可卡因和海洛因成瘾的易感基因部分重叠。
Drug addiction, a leading health problem, is a chronic brain disease with a significant genetic component. Animal models and clinical studies established the involvement of glutamate and GABA neurotransmission in drug addiction. This study was designed to assess if 258 variants in 27 genes of these systems contribute to the vulnerability to develop drug addiction. Four independent analyses were conducted in a sample of 1860 subjects divided according to drug of abuse (heroin or cocaine) and ancestry (African and European). A total of 11 SNPs in eight genes showed nominally significant associations (P < 0.01) with heroin and/or cocaine addiction in one or both ancestral groups but the associations did not survive correction for multiple testing. Of these SNPs, the GAD1 upstream SNP rs1978340 is potentially functional as it was shown to affect GABA concentrations in the cingulate cortex. In addition, SNPs GABRB3 rs7165224; DBI rs12613135; GAD1 SNPs rs2058725, rs1978340, rs2241164; and GRIN2A rs1650420 were previously reported in associations with drug addiction or related phenotypes. The study supports the involvement of genetic variation in the glutamatergic and GABAergic systems in drug addiction with partial overlap in susceptibility loci between cocaine and heroin addiction.