National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa.
Department of Health Promotion, National Institute of Public Health, Wako, Saitama, Japan.
Pharmacogenet Genomics. 2020 Apr;30(3):54-60. doi: 10.1097/FPC.0000000000000395.
This study sought to evaluate the impacts of interactions between the alcohol dehydrogenase-1B (rs1229984) genotype and the aldehyde dehydrogenase-2 (rs671) genotype on alcohol flushing, alcohol reeking on the day after drinking, and the age distribution in alcohol-dependent patients.
The study subjects were 4107 Japanese alcohol-dependent men who underwent alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotyping: 4051 patients were asked about their current or former tendency to experience facial flushing after drinking a glass of beer, and 969 patients were asked about whether they had ever been told that they reeked of alcohol more than 12 hours after they had stopped drinking.
Current, former, and never flushing were reported in 3.5, 14.9, and 81.5%, respectively, of the subject, and alcohol reeking after more than 12 hours in 36.1% of the subjects. The fast-metabolizing ADH1B*2(+) genotype (*1/2 or 2/2) and the inactive ALDH22(+) genotype (1/2 or 2/2) affected the multivariate odds ratios for current or former flushing [odds ratio, 95% confidence interval = 2.27 (1.79-2.86) and 23.0 (18.6-28.5), respectively, vs. 2(-) genotype] and for alcohol reeking [0.39 (0.29-0.52) and 1.56 (1.09-2.25), respectively, vs. 2(-) genotype]. An age-dependent decrease in the ADH1B2(-) and ALDH22(-) combination from 32.3% in the 30-39-year age group to 12.5% in the 70-79-year age group and an age-dependent increase in the ADH1B2(+) and ALDH22(-) combination from 52.5% in the 30-39-year age group to 70.5% in the 70-79-year age group were observed (P < 0.0001 for trend). The frequencies of the ADH1B2(-) and ALDH22(+) combination (4.7-6.2%) and the ADH1B2(+) and ALDH22(+) combination (8.9-12.0%) did not change markedly with increasing age.
Interactions between the alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes modified alcohol flushing, alcohol reeking on the day after drinking, and the age distribution. These findings support the protective roles of the ADH1B2(+) and ALDH22(+) genotypes against the development of alcohol dependence.
本研究旨在评估乙醇脱氢酶-1B（rs1229984）基因型和乙醛脱氢酶-2（rs671）基因型之间的相互作用对酒精性面红、饮酒后次日酒精味和酒精依赖患者年龄分布的影响。
本研究对象为 4107 名日本酒精依赖男性，进行了乙醇脱氢酶-1B 和乙醛脱氢酶-2 基因分型：4051 名患者被问及他们目前或过去是否有饮酒后出现面部潮红的倾向，969 名患者被问及他们是否曾被告知在停止饮酒 12 小时后身上有浓烈的酒精味。
当前、过去和从未出现潮红的患者分别占 3.5%、14.9%和 81.5%，超过 12 小时后仍有酒精味的患者占 36.1%。快速代谢型 ADH1B2(+)基因型（1/2 或 2/2）和无活性 ALDH22(+)基因型（1/2 或 2/2）影响了当前或过去潮红的多变量优势比[比值比，95%置信区间=2.27（1.79-2.86）和 23.0（18.6-28.5），分别为2(-)基因型]和酒精味的优势比[0.39（0.29-0.52）和 1.56（1.09-2.25），分别为2(-)基因型]。ADH1B2(-)和 ALDH22(-)组合在 30-39 岁年龄组中的比例从 32.3%逐渐下降至 70-79 岁年龄组的 12.5%，ADH1B2(+)和 ALDH22(-)组合的比例从 52.5%逐渐上升至 70-79 岁年龄组的 70.5%（P<0.0001 趋势）。ADH1B2(-)和 ALDH22(+)组合（4.7%-6.2%）和 ADH1B2(+)和 ALDH22(+)组合（8.9%-12.0%）的频率随年龄的增加没有明显变化。
乙醇脱氢酶-1B 和乙醛脱氢酶-2 基因型之间的相互作用改变了酒精性面红、饮酒后次日的酒精味和年龄分布。这些发现支持 ADH1B2(+)和 ALDH22(+)基因型对酒精依赖发展的保护作用。
