Lin S-K, Chen C-K, Ball D, Liu H-C, Loh E-W
Department of Addiction Science, Taipei City Psychiatric Center, Taipei, Taiwan.
Pharmacogenomics J. 2003;3(6):349-55. doi: 10.1038/sj.tpj.6500203.
Family and twins studies have suggested that genetic factors are involved in the development of substance use disorders. Several unrelated case/control association studies have reported associations of the GABA(A) subunit genes on 5q33 with the development of alcohol dependence. We hypothesized that these particular GABA(A) subunit genes also contribute to the development of methamphetamine use disorder. To test our hypothesis, we recruited cases using a series of questionnaires. Among the polymorphic SNPs, significant differences between cases and controls were identified in the female sample in the rs2279020 of the GABA(A)alpha1 subunit gene, and the novel SNP rs4480617 in the GABA(A)gamma2 subunit gene. No associations were found in the male sample. Further haplotype analysis identified several marker blocks significantly associated with methamphetamine use disorder in females; each block consists of the rs4480617. Our study provides preliminary evidence that the GABA(A) subunit genes on 5q33 may preferentially contribute to methamphetamine use disorder in females.
家族和双胞胎研究表明，遗传因素与物质使用障碍的发展有关。几项无关的病例/对照关联研究报告称，5q33上的GABA(A)亚基基因与酒精依赖的发展有关。我们假设这些特定的GABA(A)亚基基因也有助于甲基苯丙胺使用障碍的发展。为了验证我们的假设，我们通过一系列问卷招募了病例。在多态性单核苷酸多态性（SNP）中，在女性样本中发现GABA(A)α1亚基基因的rs2279020以及GABA(A)γ2亚基基因中的新型SNP rs4480617在病例和对照之间存在显著差异。在男性样本中未发现关联。进一步的单倍型分析确定了几个与女性甲基苯丙胺使用障碍显著相关的标记块；每个块都包含rs4480617。我们的研究提供了初步证据，表明5q33上的GABA(A)亚基基因可能优先导致女性甲基苯丙胺使用障碍。
