Search resultsGenotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B and ALDH2 gene polymorphisms
Title
Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B and ALDH2 gene polymorphisms
Publication type
Journal Article
Year of Publication
2007
Authors
Journal
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume
615
Issue
1-2
Pagination
134 - 142
Date published
2007
ISBN
00275107 (ISSN)
Keywords
acetaldehyde, ADH1B, ADH1B gene, Adult, Age Factors, Aged, alcohol, alcohol consumption, alcohol dehydrogenase, Alcohol Drinking, alcohol metabolism, Aldehyde Dehydrogenase, ALDH2, ALDH2 gene, allele, article, Asian, biological marker, controlled study, cytokinesis, DNA polymorphism, drinking behavior, Ethanol, gene, genetic algorithm, genomic instability, genotoxicity, genotype, human, human cell, Humans, Japan, Logistic Models, logistic regression analysis, Lymphocytes, male, Micronuclei, micronucleus, Micronucleus Tests, Middle Aged, Models, Genetic, Mutagens, normal human, peripheral lymphocyte, Polymorphism, Genetic, priority journal, questionnaire, smoking, smoking habit
Abstract
Ethanol is almost totally broken down by oxidative metabolism in vivo. Ethanol per se is considered to be neither carcinogenic, mutagenic nor genotoxic. However, during the metabolic conversion of ethanol to acetaldehyde and acetate, the organism is exposed to both ethanol and acetaldehyde and therefore ethanol is suspected to be co-carcinogenic. The genetic polymorphisms of alcohol dehydrogenase-2 (ADH1B) and acetaldehyde dehydrogenase-2 (ALDH2) influence the metabolism of alcohol. The ADH1B*1/*1 genotype encodes the low-activity form of ADH1B, and ALDH2*1/*2 and ALDH2*2/*2 genotype encode inactive ALDH2. The aim of this study was to test the hypothesis that polymorphisms of the ADH1B and ALDH2 genes are significantly associated with genotoxicity induced by alcohol drinking, measured using the cytokinesis-block micronucleus (CBMN) assay, an established biomarker of genome instability, in peripheral blood lymphocytes of 286 healthy Japanese men. There was a significant trend for the mean micronuclei (MN) frequency in habitual or moderate drinkers without a smoking habit to increase as the numbers of the *1 allele in ADH1B increased (P = 0.039 or P = 0.029) and the *2 allele in ALDH2 increased (P = 0.019 or P = 0.037). A logistic regression analysis showed that the number of subjects with MN frequency levels more than median value of MN (3.0) was significantly higher in the subjects with the ADH1B*1 allele as adjusted estimates (OR 2.08, 95% C.I. 1.24-3.48), when the OR for the subjects with the ADH1B*2/*2 genotype was defined as 1.00. The number of subjects with MN frequency levels more than median value of MN was also significantly higher in the subjects with the ALDH2*2 allele as adjusted estimates (OR 1.79, 95% C.I. 1.04-3.11), when the OR for the subjects with the ALDH2*1/*1 genotype was defined as 1.00. The results of this study have identified important novel associations between ADH1B/ALDH2 polymorphisms and genotoxicity in alcohol drinkers.