Polymorphisms in the glutamate decarboxylase 1 gene associated with heroin dependence.
Polymorphisms in the glutamate decarboxylase 1 gene associated with heroin dependence.
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DOI：
10.1016/j.bbrc.2012.04.112
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发表时间：
2012-05
影响因子：
3.1
通讯作者：
Weiguo Wu;Y. Zhu;S. B. Li
中科院分区：
文献类型：
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作者：
Weiguo Wu;Y. Zhu;S. B. Li
GAD 1基因编码67-kDa谷氨酸脱羧酶同种型（GAD 67），这是负责谷氨酸生物合成γ-氨基丁酸（GABA）的限速酶，可能参与药物依赖的发展。本研究通过对15个单核苷酸多态性与海洛因依赖的相关性进行分析，以确定海洛因依赖的遗传易感性（SNP，rs1978340，rs3762556，rs3791878，rs3749034，rs11542313，rs2241165，rs2241164，rs769407，rs3749033，rs16858977，rs701492，rs16858988，rs4668331，rs7578661，rs769395）的GAD 1基因的表达。参与者包括370名海洛因依赖者和389名健康对照者。海洛因依赖者rs 1978340（启动子区），rs3791878（启动子区）和rs 11542313（外显子3）多态性的等位基因或基因型频率与健康对照组有显著差异。在两个区组中观察到强烈的连锁不平衡（D′>0.9）。在海洛因依赖者中发现了显著更多的C-C-C-C-A单倍型（经Bonferroni校正后p=0.0053）和显著更少的T-C-A-C-A单倍型（经Bonferroni校正后p=0.0003）。这些发现表明GAD 1基因多态性在中国汉族海洛因依赖中的作用，并可能为今后海洛因依赖的遗传学或神经生物学研究提供信息。
The GAD1 gene encodes the 67-kDa glutamic acid decarboxylase isoform (GAD67), the rate-limiting enzyme responsible for γ-aminobutyric acid (GABA) biosynthesis from glutamic acid, and may be involved in the development of drug dependence. To identify markers contributing to the genetic susceptibility to heroin dependence, this study examined the potential association between heroin dependence and 15 single nucleotide polymorphisms (SNPs, rs1978340, rs3762556, rs3791878, rs3749034, rs11542313, rs2241165, rs2241164, rs769407, rs3749033, rs16858977, rs701492, rs16858988, rs4668331, rs7578661, rs769395) of GAD1 gene using the MassARRAY system. Participants included 370 heroin-dependent subjects and 389 healthy controls. The allelic or genotypic frequencies of the rs1978340 (promoter region), rs3791878 (promoter region), and rs11542313 (exon 3) polymorphisms in heroin addicts were significantly different from those in healthy controls. Strong linkage disequilibrium was observed in two blocks (D′>0.9). Significantly more C-C-C-C-A haplotypes (p=0.0053 after Bonferroni correction) and significantly fewer T-C-A-C-A haplotypes (p=0.0003 after Bonferroni correction) were found in heroin dependent subjects. These findings point to a role for GAD1 polymorphism in heroin dependence among Han Chinese, and may be informative for future genetic or neurobiological studies on heroin dependence.