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There are a number of epidemiological studies concerning the gender differences in the genetic etiology of alcohol dependence (AD), with ADH2 and ALDH2 being strong candidates. The purpose of this study was to investigate gender differences in frequencies of ADH2 and ALDH2 genotypes in AD patients and in a normal control (NC) group of Koreans. Study subjects consisted of 228 AD patients (180 males, 48 females) and 138 NC (79 males, 59 females). For both male and female subjects, the frequency of the ADH2*1/1 genotype was significantly higher in AD patients compared to the NC group. However, the effect size of the ADH2*1/1 genotype on AD was much larger in females than in males. Furthermore, the ALDH2*1/1 genotype was positively associated with AD in male subjects but negatively associated with AD in female patients. Interestingly, AD in males was primarily determined by ALDH2 enzyme activity (92%), whereas female AD was primarily determined by ADH2 enzyme activity (60.4%). These results suggest that risk for the development of AD in males is mainly associated with the ALDH2*1/1 genotype, while in female patients, the ADH2*1/1 genotype was more highly associated with risk of AD. Overall, it is evident that gender differences associated with genetic risks for AD are present.
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