Effect of ALDH2 and CYP2E1 Gene Polymorphisms on Drinking Behavior and Alcoholic Liver Disease in Japanese Male Workers

Abstract

Aims:We examined the relationships of ALDH2 and CYP2E1 genotypes on drinking behavior and the incidence of alcoholic liver disease in Japanese male workers.Methods: Two hundred and eighty-seven Japanese men were selected from one metal company to adjust for similar economic and social backgrounds. Drinking behavior was assessed from a self-assessment questionnaire. Genotypes of ALDH2 and CYP2E1 were analyzed with the polymerase chain reaction-single strand conformation polymorphism and with the polymerase chain reaction-restriction fragment length polymorphism, respectively.Results: The frequency of the ALDH2 genotype was 55% for typical homozygotes, 42% for heterozygotes, and 4% for atypical homozygotes. The frequency of the CYP2E1 genotype was 62% for c1 homozygotes, 35% for heterozygotes, and 3% for c2 homozygotes. The ALDH2 genotype closely influenced drinking habits, but not the CYP2E1 genotype. Among habitual drinkers, ALDH2 typical homozygotes consumed significantly larger amounts of ethanol than ALDH2 heterozygotes, whereas CYP2E1 genotypes did not influence daily alcohol consumption. Sixteen men (5.6%) were diagnosed with alcoholic liver disease. In terms of ALDH2 genotypes, 12 cases (7.6%) were typical homozygotes and 4 (3.4%) were heterozygotes, whereas the incidence of alcoholic liver disease was not different between c1/c1 homozygotes and c1/c2 heterozygotes. When the interactive contribution of the ALDH2 and CYP2E1 genotypes on drinking behavior and the incidence of alcoholic liver disease were examined, there were no significant differences in the CYP2E1 genotype among the subjects with the same ALDH2 genotype.Conclusion: The ALDH2 genotype is strongly associated with individual alcohol drinking behavior and the development of alcoholic liver disease in Japanese male workers, but the CYP2E1 genotype is not.

Genetic Polymorphisms and the Progression of Liver Fibrosis: A Critical Appraisal

“…4,[44][45][46] However, these results have not been confirmed in other investigations. 47,48 Polymorphisms in genes encoding proinflammatory cytokines known to participate in the pathogenesis of ALD have also been examined. A single nucleotide polymorphism (SNP) located in the promoter region of the TNF-␣ gene, which results in increased cytokine production, is associated with more severe steatohepatitis.…”

Differences in the Association Between Modifiable Lifestyle Factors and Gastric Precancerous Lesions Among Mongolians and Han Chinese

“…First, ALDH2*G homozygote, a genetic variation associated with heavy drinking, has been found to be more prevalent among Mongolians than Han Chinese ( 22 ). A population based study from Japan also showed that individuals with ALDH2 typical homozygote consumed significantly larger quantities of ethanol than those with ALDH2 heterozygote ( 23 ). Indeed, the possible genetic predisposition corresponds to Mongolians’ drinking patterns.…”