OBJECTIVE The risk of alcohol dependence (AD) in Japanese men and women was evaluated according to combinations of alcohol flushing and aldehyde dehydrogenase-2 (ALDH2, rs671) and alcohol dehydrogenase-1B (ADH1B, rs1229984) genotypes, all of which are known to determine AD susceptibility in Asians. Previous studies have focused on men, since women account for a smaller proportion of AD subjects. METHODS Case control studies were conducted between 3721 male and 335 female AD Japanese and 610 male and 406 female controls who were asked about their current or former tendency to experience facial flushing after drinking a glass of beer and underwent ALDH2 and ADH1B genotyping. The time at which alcohol-induced facial flushing tendencies had disappeared in former-flushing AD subjects was also evaluated. RESULTS Current alcohol flushing, the inactive ALDH2*1/*2 genotype, and the fast-metabolizing ADH1B*2 allele were less frequently found in the AD groups. Although alcohol flushing was strongly influenced by the ALDH2 and ADH1B genotypes, multiple logistic model showed that never or former flushing and the genotype combinations were independent strong risk factors of AD in men and women. Never or former flushing (vs. current flushing) markedly increased the odds ratios of AD in carriers of each of the ALDH2 and ADH1B genotype combinations. The temporal profiles for drinking and flushing in former-flushing AD subjects revealed that the flushing response disappeared soon after or before the start of habitual drinking during young adulthood, regardless of the ALDH2 genotype. CONCLUSION Although alcohol flushing is influenced by the ALDH2 and ADH1B genotypes, constitutional or acquired flushing tolerance is an independent susceptibility trait for AD. The combination of the alcohol flushing status and the ALDH2 and ADH1B genotypes can provide a better new strategy for AD risk assessment than the alcohol flushing status alone or the genotypes alone in Asian men and women.

中文翻译：

---

酒精引起的潮红与酒精和醛脱氢酶的遗传多态性的组合以及日本男性和女性酒精依赖的风险。

目的 日本男性和女性酒精依赖 (AD) 的风险是根据酒精潮红和醛脱氢酶-2 (ALDH2, rs671) 和酒精脱氢酶-1B (ADH1B, rs1229984) 基因型的组合来评估的，所有这些基因型都是已知的确定亚洲人的 AD 易感性。以前的研究主要针对男性，因为女性在 AD 受试者中所占的比例较小。方法 病例对照研究在 3721 名男性和 335 名女性 AD 日本人和 610 名男性和 406 名女性对照组之间进行，他们被问及他们目前或以前喝过一杯啤酒后面部潮红的倾向，并接受了 ALDH2 和 ADH1B 基因分型。还评估了酒精引起的面部潮红倾向在以前脸红的 AD 受试者中消失的时间。结果 目前酒精潮红，在 AD 组中较少发现失活的 ALDH2*1/*2 基因型和快速代谢的 ADH1B*2 等位基因。尽管酒精潮红受 ALDH2 和 ADH1B 基因型的强烈影响，但多重逻辑模型表明，从未或以前潮红以及基因型组合是男性和女性 AD 的独立强风险因素。从未或以前的潮红（与当前的潮红相比）显着增加了每种 ALDH2 和 ADH1B 基因型组合携带者中 AD 的优势比。前脸红的 AD 受试者饮酒和脸红的时间分布显示，无论 ALDH2 基因型如何，在成年早期开始习惯性饮酒之后或之前，脸红反应很快消失。结论 虽然酒精潮红受 ALDH2 和 ADH1B 基因型的影响，体质性或获得性潮红耐受性是 AD 的独立易感性特征。在亚洲男性和女性中，酒精潮红状态与 ALDH2 和 ADH1B 基因型的组合可以为 AD 风险评估提供比单独的酒精潮红状态或单独的基因型更好的新策略。