Hines L M, Stampfer M J, Ma J, Gaziano J M, Ridker P M, Hankinson S E, Sacks F, Rimm E B, Hunter D J
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
N Engl J Med. 2001 Feb 22;344(8):549-55. doi: 10.1056/NEJM200102223440802.
A polymorphism in the gene for alcohol dehydrogenase type 3 (ADH3) alters the rate of alcohol metabolism. We investigated the relation among the ADH3 polymorphism, the level of alcohol consumption, and the risk of myocardial infarction in a nested case-control study based on data from the prospective Physicians' Health Study.
We identified 396 patients with eligible newly diagnosed cases of myocardial infarction among men in the Physicians' Health Study. Of these patients, 374 were matched with 2 randomly selected control subjects each and the remaining 22 with 1 control each (total, 770 controls). The ADH3 genotype (gamma1gamma1, gamma1gamma2, or gamma2gamma2) was determined in all subjects. We examined the relations among the level of alcohol intake, the ADH3 genotype, and plasma high-density lipoprotein (HDL) levels in this study population and in a similar cohort of women.
As compared with homozygosity for the allele associated with a fast rate of ethanol oxidation (gamma1), homozygosity for the allele associated with a slow rate of ethanol oxidation (gamma2) was associated with a reduced risk of myocardial infarction (relative risk, 0.65; 95 percent confidence interval, 0.43 to 0.99). Moderate alcohol consumption was associated with a decreased risk of myocardial infarction in all three genotype groups (gamma1gamma1, gamma1gamma2, and gamma2gamma2); however, the ADH3 genotype significantly modified this association (P=0.01 for the interaction). Among men who were homozygous for the gamma1 allele, those who consumed at least one drink per day had a relative risk of myocardial infarction of 0.62 (95 percent confidence interval, 0.34 to 1.13), as compared with the risk among men who consumed less than one drink per week. Men who consumed at least one drink per day and were homozygous for the gamma2 allele had the greatest reduction in risk (relative risk, 0.14; 95 percent confidence interval, 0.04 to 0.45). Such men also had the highest plasma HDL levels (P for interaction = 0.05). We confirmed the interaction among the ADH3 genotype, the level of alcohol consumption, and the HDL level in an independent study of postmenopausal women (P=0.02).
Moderate drinkers who are homozygous for the slow-oxidizing ADH3 allele have higher HDL levels and a substantially decreased risk of myocardial infarction.
3型乙醇脱氢酶（ADH3）基因的多态性会改变酒精代谢速率。我们基于前瞻性医生健康研究的数据，在一项巢式病例对照研究中调查了ADH3多态性、饮酒量与心肌梗死风险之间的关系。
我们在医生健康研究中的男性中确定了396例符合条件的新诊断心肌梗死患者。其中，374例患者分别与2名随机选择的对照受试者匹配，其余22例患者各与1名对照匹配（共770名对照）。测定了所有受试者的ADH3基因型（γ1γ1、γ1γ2或γ2γ2）。我们在该研究人群以及一组类似的女性队列中研究了饮酒量、ADH3基因型和血浆高密度脂蛋白（HDL）水平之间的关系。
与乙醇氧化速率快相关等位基因的纯合子（γ1）相比，乙醇氧化速率慢相关等位基因的纯合子（γ2）与心肌梗死风险降低有关（相对风险为0.65；95%置信区间为从0.43至0.99）。在所有三个基因型组（γ1γ1、γ1γ2和γ2γ2）中，适度饮酒都与心肌梗死风险降低有关；然而，ADH3基因型显著改变了这种关联（交互作用P = 0.01）。在γ1等位基因纯合的男性中，每天至少饮用一杯酒的男性心肌梗死相对风险为0.62（95%置信区间为从0.34至1.13），而每周饮酒少于一杯的男性。每天至少饮用一杯酒且为γ2等位基因纯合的男性风险降低幅度最大（相对风险为0.14；95%置信区间为从0.04至0.45）。这类男性的血浆HDL水平也最高（交互作用P = 0.05）。我们在一项关于绝经后女性的独立研究中证实了ADH3基因型、饮酒量和HDL水平之间的交互作用（P = 0.02）。
ADH3慢氧化等位基因纯合的适度饮酒者HDL水平较高，心肌梗死风险大幅降低。
