The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence.
The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence.
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DOI：
10.1016/j.biopsych.2009.08.019
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发表时间：
2010-01-01
影响因子：
10.6
通讯作者：
Roy, Alec
中科院分区：
文献类型：
--
作者：
Enoch, Mary-Anne;Hodgkinson, Colin A.;Yuan, Qiaoping;Shen, Pei-Hong;Goldman, David;Roy, Alec
关键词：
GABRA2基因与成瘾有关。早期生活压力已被证明会改变成年啮齿动物中GABRA2的表达。我们假设童年创伤、GABRA2变异及其相互作用会影响成瘾脆弱性。本研究招募了非裔美国男性：577名终身DSM-IV诊断为酒精、可卡因和海洛因依赖的单一和合并症患者，以及255名对照组。采用儿童创伤问卷（CTQ）。10个GABRA2单倍型标记snp进行基因分型。我们发现暴露于童年创伤预测物质依赖（p < 0.0001）。多物质依赖与CTQ评分最高相关（p < 0.0001）。非洲裔美国人在远端单倍型区有四个常见的单倍型（频率：0.11 - 0.30）：两个与高加索人和亚洲人的阴阳单倍型相对应，另外两个在其他种族中没有发现。其中一种独特的单倍型预测海洛因成瘾，而另一种单倍型在对照组中更为常见，似乎赋予了在遭受严重童年创伤后对成瘾的恢复能力。阴阳单倍型没有影响。此外，内含子2 SNP rs11503014不位于任何单倍型区，可能与外显子剪接有关，与成瘾，特别是海洛因成瘾独立相关（p < 0.005）。童年创伤与rs11503014变异相互作用，影响成瘾脆弱性，特别是对可卡因（p < 0.005）。我们的研究结果表明，至少在非裔美国男性中，童年创伤、GABRA2变异及其相互作用在物质依赖的风险恢复能力中起作用。
The GABRA2 gene has been implicated in addiction. Early life stress has been shown to alter GABRA2 expression in adult rodents. We hypothesized that childhood trauma, GABRA2 variation and their interaction would influence addiction vulnerability. African American men were recruited for this study: 577 patients with lifetime DSM-IV single and comorbid diagnoses of alcohol, cocaine and heroin dependence, and 255 controls. The Childhood Trauma Questionnaire (CTQ) was administered. Ten GABRA2 haplotype-tagging SNPs were genotyped. We found that exposure to childhood trauma predicted substance dependence (p < 0.0001). Polysubstance dependence was associated with the highest CTQ scores (p < 0.0001). The African Americans had four common haplotypes (frequency: 0.11 – 0.30) within the distal haplotype block: two that correspond to the Caucasian and Asian yin-yang haplotypes and two not found in other ethnic groups. One of the unique haplotypes predicted heroin addiction whereas the other haplotype was more common in controls and appeared to confer resilience to addiction after exposure to severe childhood trauma. The yin-yang haplotypes had no effects. Moreover, the intron 2 SNP rs11503014, not located in any haplotype block and potentially implicated in exon splicing, was independently associated with addiction, specifically heroin addiction (p < 0.005). Childhood trauma interacted with rs11503014 variation to influence addiction vulnerability, particularly to cocaine (p < 0.005). Our results suggest that at least in African American men, childhood trauma, GABRA2 variation and their interaction play a role in risk-resilience for substance dependence.
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影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
DOI：
10.1097/00004583-199703000-00012
发表时间：
1997-03-01
影响因子：
13.3
作者：
Bernstein, DP;Ahluvalia, T;Handelsman, L
通讯作者：
Handelsman, L
影响因子：
6.9
作者：
Fergusson, DM;Horwood, LJ;Woodward, LJ
通讯作者：
Woodward, LJ
影响因子：
56.9
作者：
DODGE, KA;BATES, JE;PETTIT, GS
通讯作者：
PETTIT, GS
影响因子：
4.8
作者：
Bernstein, DP;Stein, JA;Zule, W
通讯作者：
Zule, W