Background: Previous studies have suggested a genetic predisposition to the development of Wernicke-Korsakoff syndrome (WKS), a neuropsychiatric syndrome commonly associated with alcoholism; however, little is known about this genetic risk factor. Methods: To test the hypothesis that altered alcohol or aldehyde regulation is related to the development of WKS, the genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-2 (ADH2) were examined in 47 alcoholic subjects with WKS and compared with those of 342 alcoholic subjects without any WKS symptoms and 175 nonalcoholic controls. Results: Although the frequencies of the ALDH2 genotypes and alleles did not differ significantly between alcoholic subjects with WKS and alcoholics without WKS, the ADH2*1/2*1 genotype and ADH2*1 allele were significantly increased in WKS. Conclusions: These findings suggest that the ADH2*1/2*1 genotype is a risk factor for the development of WKS in alcoholic patients.
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