Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Alcohol Clin Exp Res. 2013 Nov;37(11):1872-81. doi: 10.1111/acer.12176. Epub 2013 Jul 29.
Alcohol dehydrogenase 1B and 1C (ADH1B and ADH1C) variants have been robustly associated with alcohol phenotypes in East Asian populations, but less so in non-Asian populations where prevalence of the most protective ADH1B allele is low (generally <5%). Further, the joint effects of ADH1B and ADH1C on alcohol phenotypes have been unclear. Therefore, we tested the independent and joint effects of ADH1B and ADH1C on alcohol phenotypes in an Israeli sample, with higher prevalence of the most protective ADH1B allele than other non-Asian populations.
A structured interview assessed lifetime drinking and alcohol use disorders (AUDs) in adult Israeli household residents. Four single nucleotide polymorphisms (SNPs) were genotyped: ADH1B (rs1229984, rs1229982, and rs1159918) and ADH1C (rs698). Regression analysis examined the association between alcohol phenotypes and each SNP (absence vs. presence of the protective allele) as well as rs698/rs1229984 diplotypes (also indicating absence or presence of protective alleles) in lifetime drinkers (n = 1,129).
Lack of the ADH1B rs1229984 protective allele was significantly associated with consumption- and AUD-related phenotypes (OR = 1.77 for AUD; OR = 1.83 for risk drinking), while lack of the ADH1C rs698 protective allele was significantly associated with AUD-related phenotypes (OR = 2.32 for AUD). Diplotype analysis indicated that jointly ADH1B and ADH1C significantly influenced AUD-related phenotypes. For example, among those without protective alleles for ADH1B or ADH1C, OR for AUD was 1.87 as compared to those without the protective allele for ADH1B only and was 3.16 as compared to those with protective alleles for both ADH1B and ADH1C.
This study adds support for the relationship of ADH1B and ADH1C and alcohol phenotypes in non-Asians. Further, these findings help clarify the mixed results from previous studies by showing that ADH1B and ADH1C jointly effect AUDs, but not consumption. Studies of the association between alcohol phenotypes and either ADH1B or ADH1C alone may employ an oversimplified model, masking relevant information.
在东亚人群中，乙醇脱氢酶 1B 和 1C（ADH1B 和 ADH1C）变体与酒精表型之间存在很强的关联，但在非亚洲人群中关联程度较低，因为这些人群中最具保护作用的 ADH1B 等位基因的流行率较低（一般<5%）。此外，ADH1B 和 ADH1C 对酒精表型的联合作用尚不清楚。因此，我们在以色列样本中测试了 ADH1B 和 ADH1C 对酒精表型的独立和联合作用，该样本中具有较高比例的最具保护作用的 ADH1B 等位基因，高于其他非亚洲人群。
通过结构化访谈评估成年以色列居民的终生饮酒和酒精使用障碍（AUD）情况。共检测了 4 个单核苷酸多态性（SNP）：ADH1B（rs1229984、rs1229982 和 rs1159918）和 ADH1C（rs698）。回归分析检测了在终生饮酒者（n=1129）中，每个 SNP（保护性等位基因的存在或缺失）以及 rs698/rs1229984 双等位基因（也指示保护性等位基因的存在或缺失）与酒精表型之间的关联。
缺乏 ADH1B rs1229984 保护性等位基因与饮酒和 AUD 相关表型显著相关（OR=1.77 用于 AUD；OR=1.83 用于风险饮酒），而缺乏 ADH1C rs698 保护性等位基因与 AUD 相关表型显著相关（OR=2.32 用于 AUD）。双等位基因分析表明，ADH1B 和 ADH1C 共同显著影响 AUD 相关表型。例如，在没有 ADH1B 或 ADH1C 保护性等位基因的个体中，AUD 的 OR 值为 1.87，而在仅缺乏 ADH1B 保护性等位基因的个体中为 1.87，而在同时具有 ADH1B 和 ADH1C 保护性等位基因的个体中为 3.16。
本研究为非亚洲人群中 ADH1B 和 ADH1C 与酒精表型之间的关系提供了更多支持。此外，这些发现通过表明 ADH1B 和 ADH1C 共同影响 AUD，而不是饮酒，有助于澄清先前研究中混杂的结果。研究 ADH1B 或 ADH1C 与酒精表型的单一关联可能采用了过于简化的模型，掩盖了相关信息。
