GABRA2 markers moderate the subjective effects of alcohol.
GABRA2 markers moderate the subjective effects of alcohol.
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DOI：
10.1111/j.1369-1600.2012.00457.x
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发表时间：
2013-03
影响因子：
3.4
通讯作者：
Wand GS
中科院分区：
文献类型：
--
作者：
Uhart M;Weerts EM;McCaul ME;Guo X;Yan X;Kranzler HR;Li N;Wand GS
对酒精的主观反应（SR）的个体差异受遗传变异的调节，可能是酒精使用障碍发展的风险因素。GABAA α2受体亚基基因（GABRA 2）的变异与酒精依赖（AD）有关。因此，我们研究了SR的个体差异是否与GABRA 2的变化有关，SR反映了对酒精影响的敏感性。69名健康受试者（21-30岁）接受了基于实验室的会话内累积口服酒精给药程序，达到平均峰值血液酒精水平为100.4 mg/dL（SE =2.5）。在整个过程中获得主观评估，包括酒精曲线的上升和下降分支。我们对跨越GABRA 2的4号染色体区域的单核苷酸多态性（SNP）进行基因分型，并分析基因型和单倍型对酒精主观反应的影响。群体亚结构的特点是通过使用祖先信息标记。个体SNP分析表明，SNP rs 279858、rs 279844、rs 279845、rs 279826、rs 279828和rs 279836的次要等位基因携带者的“负”酒精效应得分低于每个SNP的共同等位基因纯合子个体（分别为p=0.0060、p= 0.0035、p = 0.0045、p=0.0043、p=0.0037、p=0.0061）。区块1的单倍型效应显示与该区块中的SNP一致的结果（对于单倍型1和4，分别为p=0.0492和p=0.0150）。这些SNP中的几个的次要等位基因先前已与AD相关。我们的研究结果提供了进一步的证据表明，GABRA 2内的变异与对酒精的负面反应减弱有关，这是一种已知的易患酒精使用障碍的风险因素。
Individual differences in subjective responses to alcohol (SR) are moderated by genetic variants and may be risk factors for the development of alcohol use disorders. Variation in the GABAA α2 receptor subunit gene (GABRA2) has been associated with alcohol dependence (AD). Therefore, we examined whether individual differences in SR, which reflect sensitivity to the effects of alcohol, are associated with variation in GABRA2. Sixty-nine healthy subjects (21–30 yr) underwent a laboratory-based within-session, cumulative oral alcohol dosing procedure, achieving a mean peak blood alcohol level of 100.4 mg/dL (SE =2.5). Subjective assessments were obtained throughout the session, including ascending and descending limbs of the alcohol curve. We genotyped single nucleotide polymorphisms (SNPs) across the chromosome 4 region spanning GABRA2 and analyzed the effect of genotype and haplotypes on subjective responses to alcohol. Population substructure was characterized through the use of ancestry informative markers. Individual SNP analysis demonstrated that carriers of the minor alleles for SNPs rs279858, rs279844, rs279845, rs279826, rs279828 and rs279836 had lower “Negative” alcohol effects scores than individuals homozygous for the common allele at each SNP (p=0.0060, p=0.0035, p=0.0045, p=0.0043, p=0.0037, p=0.0061, respectively). Haplotype effects of block 1 showed concordant results with SNPs in this block (p=0.0492 and p=0.0150 for haplotypes 1 and 4, respectively). The minor alleles for several of these SNPs have previously been associated with AD. Our findings provide further evidence that variation within GABRA2 is associated with attenuated negative responses to alcohol, a known risk factor for vulnerability to alcohol use disorders.
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DOI：
10.1038/npp.2008.171
发表时间：
2009-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.6
作者：
Dick, DM;Jones, K;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
DOI：
10.1002/ajmg.b.30091
发表时间：
2004-08-15
影响因子：
2.8
作者：
Covault, J;Gelernter, J;Kranzler, HR
通讯作者：
Kranzler, HR