Department of Psychiatry, School of Medicine, Yale University, 300 George Street, Suite 503, New Haven, CT 06511, USA.
Hum Genet. 2012 Aug;131(8):1361-74. doi: 10.1007/s00439-012-1163-5. Epub 2012 Apr 5.
The alcohol dehydrogenase 1C (ADH1C) subunit is an important member of the alcohol dehydrogenase family, a set of genes that plays a major role in the catabolism of ethanol. Numerous association studies have provided compelling evidence that ADH1C gene variation (formerly ADH3) is associated with altered genetic susceptibility to alcoholism and alcohol-related liver disease, cirrhosis, or pancreatitis. However, the results have been inconsistent, partially, because each study involved a limited number of subjects, and some were underpowered. Using cumulative data over the past two decades, this meta-analysis (6,796 cases and 6,938 controls) considered samples of Asian, European, African, and Native American origins to examine whether the aggregate genotype provide statistically significant evidence of association. The results showed strong evidence of association between ADH1C Ile350Val (rs698, formerly ADH1C *1/*2) and alcohol dependence (AD) and abuse in the combined studies. The overall allelic (Val vs. Ile or *2 vs. *1) P value was 1 × 10(-8) and odds ratio (OR) was 1.51 (1.31, 1.73). The Asian populations produced stronger evidence of association with an allelic P value of 4 × 10(-33) [OR 2.14 (1.89, 2.43)] with no evidence of heterogeneity, and the dominant and recessive models revealed even stronger effect sizes. The strong evidence remained when stricter criteria and sub-group analyses were applied, while Asians always showed stronger associations than other populations. Our findings support that ADH1C Ile may lower the risk of AD and alcohol abuse as well as alcohol-related cirrhosis in pooled populations, with the strongest and most consistent effects in Asians.
醇脱氢酶 1C（ADH1C）亚基是醇脱氢酶家族的重要成员，该基因家族在乙醇的分解代谢中起着主要作用。大量的关联研究提供了令人信服的证据，表明 ADH1C 基因变异（以前称为 ADH3）与酗酒和与酒精相关的肝病、肝硬化或胰腺炎的遗传易感性改变有关。然而，结果并不一致，部分原因是每项研究涉及的研究对象数量有限，而且有些研究的效力不足。本荟萃分析（6796 例病例和 6938 例对照）利用过去二十年来的累积数据，考虑了亚洲、欧洲、非洲和美洲原住民的样本，以检验总体基因型是否提供了与关联有统计学意义的证据。结果表明，ADH1C Ile350Val（rs698，以前称为 ADH1C *1/*2）与酒精依赖（AD）和滥用在合并研究中存在很强的关联证据。总体等位基因（Val 对 Ile 或 *2 对 *1）P 值为 1×10(-8)，优势比（OR）为 1.51（1.31，1.73）。亚洲人群的关联证据更强，等位基因 P 值为 4×10(-33)[OR 2.14（1.89，2.43）]，无异质性，显性和隐性模型显示出更强的效应大小。当应用更严格的标准和亚组分析时，这种强有力的证据仍然存在，而亚洲人始终表现出比其他人群更强的关联。我们的研究结果支持 ADH1C Ile 可能降低了 AD 和酒精滥用以及在混合人群中与酒精相关的肝硬化的风险，在亚洲人群中效果最强且最一致。
