Alcohol dehydrogenase 2 His47 Arg polymorphism influences drinking habit independently of aldehyde dehydrogenase 2 Glu487 Lys polymorphism:: Analysis of 2,299 Japanese subjects
Alcohol dehydrogenase 2 His47 Arg polymorphism influences drinking habit independently of aldehyde dehydrogenase 2 Glu487 Lys polymorphism:: Analysis of 2,299 Japanese subjects
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DOI：
10.1158/1055-9965.epi-05-0911
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发表时间：
2006-05-01
影响因子：
3.8
通讯作者：
Tajima, Kazuo
中科院分区：
文献类型：
--
作者：
Matsuo, Keitaro;Wakai, Kenji;Tajima, Kazuo
尽管乙醇脱氢酶2(ADH2)His(47)Arg基因多态性的功能作用已被阐明，但其在习惯性饮酒中的作用仍不清楚。在这里，我们对2299名非酒精日本受试者(989名男性和1310名女性)进行了一项横断面研究。通过ADH2和乙醛脱氢酶2(ALDH2)基因多态性检测饮酒情况、酒精摄入量和对一杯啤酒的物理反应。通过年龄、性别、吸烟状况和基因调整的优势比及其95%的可信区间来评估关联的强度。ADH2、His/Arg、Arg/Arg等位基因携带者习惯性饮酒的危险性较高。在男性中，ALDH2型和混杂因素调整后的优势比(95%可信区间)分别为1.3(0.89-1.89)和3.16(1.03-9.70)，这一趋势具有统计学意义(P=0.024)。在女性中也观察到类似的趋势。ALDH2Glu/Lys两种多态的联合基因分型结果显示，ADH2Arg等位基因对ALDH2Glu/Lys携带者有明显的影响(P趋势=0.007，女性为0.024)。与其他ADH2基因型相比，Arg/Arg携带者的身体反应，如潮红和心悸明显较少，当与ALDH2 Glu/Lys联合使用时，这一点尤为明显。大量饮酒也与ADH2 Arg等位基因密切相关。综上所述，本研究显示ADH2 His(47)Arg多态性对习惯性饮酒的影响与ALDH2基因型无关。
Although the functional effect of alcohol dehydrogenase 2 (ADH2) HiS(47)Arg polymorphism has been elucidated, its effect on habitual drinking remains unknown. Here, we conducted a cross-sectional study in 2,299 nonalcoholic Japanese subjects (989 men and 1,310 women). Drinking status, ethanol consumption, and physical reaction to one glass of beer were examined with regard to ADH2 and aldehyde dehydrogenase 2 (ALDH2) polymorphism. Strength of associations were assessed by age-, sex-, smoking status-, and genotype-adjusted odds ratios and their 95% confidence intervals. ADH2 His/Arg and Arg/Arg genotypes showed higher risk for habitual drinking. Among men, ALDH2 genotype- and confounder-adjusted odds ratios (95% confidence intervals) were 1.30 (0.89-1.89) and 3.16 (1.03-9.70), and this trend was significant (P = 0.024). A similar trend was observed among women. The combination genotypes of two polymorphisms revealed the clear effect of the ADH2 Arg allele among those with ALDH2 Glu/Lys in both sexes (P-trend = 0.007 for men and 0.024 for women). Physical reactions, such as flushing and palpitation, were significantly less common in those with Arg/Arg compared with other ADH2 genotypes, and this was marked when combined with ALDH2 Glu/Lys. Heavy drinker status was also strongly associated with ADH2 Arg alleles. In conclusion, this study showed the strong effect of ADH2 HiS(47)Arg polymorphism on habitual drinking regardless of ALDH2 genotype.