This study investigated the association of ADH1B (rs1229984) and ALDH2 (rs671) polymorphisms with glucose tolerance status, as determined by a 75-g oral glucose tolerance test, and effect modification of these polymorphisms on the association between alcohol consumption and glucose intolerance in male officials of the Self-Defense Forces. The study subjects included 1520 men with normal glucose tolerance, 553 with prediabetic condition (impaired fasting glucose and impaired glucose tolerance), and 235 men with type 2 diabetes. There was an evident interaction between alcohol consumption and ADH1B polymorphism in relation to type 2 diabetes (interaction ). The ALDH2 Lys allele was associated with a decreased prevalence odds of type 2 diabetes regardless of alcohol consumption. In conclusion, the ADH1B polymorphism modified the association between alcohol consumption and type 2 diabetes. A positive association between alcohol consumption and type 2 diabetes was confounded by ALDH2 polymorphism. 1. Introduction Moderate alcohol consumption has generally been associated with decreased risk of type 2 diabetes, as summarized in a meta-analysis of 15 prospective cohort studies [1]. However, the results from these studies are not necessarily consistent, especially regarding high alcohol consumption and diabetes risk. While several studies showed a U-shaped relationship between alcohol and diabetes risk [1], others reported increased risks of type 2 diabetes in alcohol consumption categories of 25？g/day [2], 40？g/day [3], and 3 drinks per day [4]. Another study found a progressive decrease in the risk of type 2 diabetes up to a consumption of 50？g of alcohol per day [5]. The inconsistent results may be ascribed to differences in ascertainment of alcohol consumption and diabetes mellitus among studies and different genetic susceptibilities to alcohol exposure among study populations. Ethanol is first oxidized to acetaldehyde by alcohol dehydrogenase (ADH), and acetaldehyde is further metabolized to acetate by aldehyde dehydrogenase (ALDH). Human ADH exhibits several isoenzymes, and functional polymorphisms are known for the ADH1B and ADH1C genes [6, 7]. The ADH1B Arg47His polymorphism (rs1229984) affects the enzyme activity substantially, and the ADH1B*47His allele (alternatively ADH2*2) is associated with faster oxidation. The ADH1C Ile349Val polymorphism (rs698) influences ADH activity to a lesser extent, and the ADH1C*349Ile allele (alternatively ADH3*1) is associated with moderately faster oxidation [8]. The ADH1B*47His allele is the major allele in Asians
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