Association of alcohol dehydrogenase 2*1 allele with liver damage and insulin concentration in the Japanese
Association of alcohol dehydrogenase 2*1 allele with liver damage and insulin concentration in the Japanese
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DOI：
10.1007/s10038-005-0318-9
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Ohta, S
中科院分区：
文献类型：
--
作者：
Suzuki, Y;Ando, F;Ohta, S
日本人在乙醇脱氢酶2基因（ADH 2）上存在多态性。ADH 2的等位基因（ADH 2 *1和ADH 2 *2）分别编码乙醇代谢的活性较高和活性较低的形式。我们研究了日本人的肝脏损伤和胰岛素-葡萄糖轴是否根据ADH 2基因型而变化。2，232名受试者（1，126名男性和1，106名女性）是从基于人群的前瞻性队列研究中招募的。比较ADH 2基因型之间的临床评价，包括饮酒量、饮酒者百分比、血糖、HbA 1c、胰岛素、AST、ALT、γ-GTP和糖尿病患病率。ADH 2 *1/1组饮酒率、饮酒量、AST、ALT、γ-GTP均高于ADH 2 *1/2组和ADH 2 *2/2组（均P < 0.05）。因此，ADH 2 *1/1与过量饮酒和肝脏疾病有关。然而，糖尿病的患病率在三组之间没有差异。对于葡萄糖-胰岛素轴，我们检查了未接受胰岛素治疗或口服抗糖尿病药物的受试者。ADH*1/2和ADH 2 *2/2的饮酒量和葡萄糖水平几乎相同，但ADH 2 *2/1的胰岛素浓度低于ADH 2 *2/2（男性P < 0.05）。这一发现表明，ADH 2 *1等位基因与低胰岛素浓度相关时，酒精摄入量是轻或中度。这也表明ADH 2 *1的遗传效应在饮酒行为和肝损伤的发生中起着重要作用，但这种作用是如此轻微，以至于它不影响葡萄糖-胰岛素轴或糖尿病的患病率。
The Japanese have a polymorphism in the alcohol dehydrogenase 2 gene (ADH2). The alleles of ADH2 (ADH2*1 and ADH2*2) encode more active and less active forms for ethanol metabolism, respectively. We examined whether liver damage and the insulin-glucose axis vary according to ADH2 genotype in the Japanese. The 2,232 Subjects (1,126 men and 1,106 women) were recruited from a population-based prospective cohort study. Clinical evaluations including alcohol consumption, percentage of alcohol drinkers, plasma glucose, HbA1c, Insulin, AST, ALT, gamma-GTP, and prevalence of diabetes were compared among the ADH2 genotypes. The percentage of drinkers, alcohol consumption, AST, ALT, and gamma-GTP were higher in group ADH2*1/1 than in group ADH2*1/2 or ADH2*2/2 (all P < 0.05). Hence, ADH2*1/1 is associated with excess alcohol intake and liver disorders. However, the prevalence of diabetes did not differ among the three groups. For the glucose-insulin axis, we examined subjects who did not receive insulin therapy or oral anti-diabetes medication. While amounts of alcohol consumed and glucose levels were nearly the same between ADH*1/2 and ADH2*2/2, insulin concentrations were lower in ADH2*2/1 than in ADH2*2/2 (P < 0.05 in men). This finding suggests that the ADH2*1 allele is associated with a lower insulin concentration when alcohol intake is light or moderate. It also suggests that the genetic effect of ADH2*1 plays an important role in alcohol drinking behavior and in the occurrence of liver injury, but the effect is so mild that it does not influence the glucose-insulin axis or prevalence of diabetes.