Fischer Monika, Wetherill Leah Flury, Carr Lucinda G, You Min, Crabb David W
Department of Medicine, Indiana University School of Medicine and the Richard Roudebush Veteran's Affairs Medical Center, Indianapolis, Indiana, USA.
Alcohol Clin Exp Res. 2007 Oct;31(10):1654-9. doi: 10.1111/j.1530-0277.2007.00471.x.
Reduction in activity of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) enzyme due to genetic deficiency causes reactions related to alcohol consumption and lowers the risk of alcoholism. ALDH2*2 is the only functionally significant polymorphism of the ALDH2 gene. An additional polymorphic locus in the promoter (G to A substitution approximately 360 bp from the translation start site) may influence ALDH2 activity through effects on transcriptional activity. The A allele is predicted to be less active transcriptionally than the G allele. Therefore, we hypothesized that individuals with 1 or 2 A alleles would have exaggerated reactions to alcohol.
Fifty-three Jewish college students from a Midwestern University and 76 Jewish individuals living in a large Midwestern city (all of Ashkenazi descent) were tested for associations between ALDH2G and ALDH2A alleles and self-reported alcohol consumption and responses to alcohol. Genotype determination was performed using PCR and slot-blot hybridization. As alcohol drinking behavior differed substantially between the college students and the general population, as well as between males and females, the analyses were performed separately in each group.
The frequency of the ALDH2A allele was 0.87 in the 129 Jewish individuals tested. Among the general Jewish population, those who were homozygous for ALDH2A drank fewer drinks per occasion than individuals who were not homozygous for the ALDH2*A allele, but did not drink significantly less frequently. When the other covariates (ADH1B genotype, gender, and population) were controlled for, there was a marginal association between ALDH2A genotype and quantity of alcohol consumed and the number of drinks consumed before feeling drowsy.
This study suggests that the ALDH2*A allele status may correlate with variations in alcohol consumption patterns among Jews, independent of the effect of ADH1B genotype.
由于基因缺陷导致线粒体乙醛脱氢酶2（ALDH2）活性降低会引发与饮酒相关的反应，并降低酗酒风险。ALDH2*2是ALDH2基因唯一具有功能意义的多态性。启动子中的另一个多态性位点（翻译起始位点约360 bp处的G到A替换）可能通过影响转录活性来影响ALDH2活性。预计A等位基因在转录上的活性低于G等位基因。因此，我们假设携带1个或2个A等位基因的个体对酒精会有更强烈的反应。
对来自中西部一所大学的53名犹太大学生和居住在中西部一个大城市的76名犹太个体（均为阿什肯纳兹血统）进行测试，以研究ALDH2G和ALDH2A等位基因与自我报告的饮酒情况及对酒精的反应之间的关联。使用聚合酶链反应（PCR）和狭缝印迹杂交进行基因型测定。由于大学生与普通人群之间以及男性和女性之间的饮酒行为存在很大差异，因此在每组中分别进行分析。
在接受测试的129名犹太个体中，ALDH2A等位基因的频率为0.87。在普通犹太人群中，ALDH2A纯合子每次饮酒的量比非ALDH2*A等位基因纯合子少，但饮酒频率并无显著降低。在控制了其他协变量（乙醇脱氢酶1B（ADH1B）基因型、性别和人群）后，ALDH2A基因型与饮酒量以及感到困倦前饮用的饮料数量之间存在微弱关联。
本研究表明，ALDH2*A等位基因状态可能与犹太人饮酒模式的差异相关，且独立于ADH1B基因型的影响。
