Role of GABRA2 on risk for alcohol, nicotine, and cannabis dependence in the Iowa Adoption Studies.
Role of GABRA2 on risk for alcohol, nicotine, and cannabis dependence in the Iowa Adoption Studies.
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DOI：
10.1097/ypg.0b013e3283208026
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发表时间：
2009-04
影响因子：
0.9
通讯作者：
Adams W
中科院分区：
文献类型：
--
作者：
Philibert RA;Gunter TD;Beach SR;Brody GH;Hollenbeck N;Andersen A;Adams W
许多研究表明，GABRA2的遗传变异改变了酒精依赖的脆弱性。然而，因果变量的确切身份，这些变量与其他形式的物质使用和行为疾病的关系尚不确定。因此，我们对来自爱荷华州收养研究（一项关于物质使用的大型纵向病例和对照收养研究）的516名受试者进行了包括GABRA2基因座在内的39个单核苷酸多态性的基因分型，并分析了他们一生中三种常见形式物质使用的历史（酒精（AD）、尼古丁（ND）和大麻依赖（CD））、重性抑郁症（MDD）和反社会人格障碍（ASPD）以及相关暴露变量。使用回归分析，我们发现大量的证据表明，GABRA2基因型和单倍型显着相关的脆弱性，AD，ND和CD与ND的关系最密切。与先前的研究表明暴露是物质使用发展的重要一步相一致，我们发现将物质暴露数据纳入我们的分析模型显着增加了GABRA2单倍型与物质使用的遗传关联的强度。最后，我们报告说，遗传效应在女性比男性明显更明显。我们的结论是，GABRA2基因座或附近的遗传变异显着影响脆弱性不仅AD，但其他形式的物质使用，包括ND和CD，这种影响可能是性别依赖性的。
A number of studies have demonstrated that genetic variation at GABRA2 alters vulnerability to alcohol dependence. However, the exact identity of the causal variant(s), the relationship of these variants to other forms of substance use and behavioral illness is uncertain. Therefore, we genotyped 516 subjects from the Iowa Adoption Studies, a large longitudinal case and control adoption study of substance use, at 39 single nucleotide polymorphisms encompassing the GABRA2 locus and analyzed them with respect to their lifetime history of three common forms of substance use (alcohol (AD), nicotine (ND) and cannabis dependence (CD)), major depressive disorder (MDD) and antisocial personality disorder (ASPD) and relevant exposure variables. Using regression analysis, we found substantial evidence that both GABRA2 genotype and haplotype are significantly related to vulnerability to AD, ND and CD with the strongest relationships noted with respect to ND. Consistent with prior studies suggesting exposure is an important step in the development of substance use, we found the inclusion of substance exposure data in to our analytic models markedly increased the strength of the genetic associations of GABRA2 haplotype with substance use. Finally, we report that the genetic effects were markedly more pronounced in females than in males. We conclude that genetic variation at or near the GABRA2 locus significantly effects vulnerability not only to AD, but to other forms of substance use including ND and CD, and that the effects may be sex dependent.