Mutation Research 541 (2003) 71–80 Effects of ALDH2 gene polymorphisms and alcohol-drinking behavior on micronuclei frequency in non-smokers Hitoshi Ishikawa a,∗ , Hidetaka Yamamoto b , Ying Tian a , Mitsuo Kawano c , Toru Yamauchi a , Kazuhito Yokoyama a a Department of Public Health and Preventive Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu 514-8507, Japan b Department of Forensic Medicine and Sciences, Mie University School of Medicine, Edobashi 2-174, Tsu 514-8507, Japan c Department of Microbiology, Mie University School of Medicine, Edobashi 2-174, Tsu 514-8507, Japan Received 16 May 2003; received in revised form 25 July 2003; accepted 25 July 2003 Abstract Alcohol abuse is a serious health problem, leading to life-threatening damage to most of the important organ systems. Genotoxic damage is used as an early effect indicator in the surveillance of human exposure to genotoxic substances. Intra- and inter-individual variations of baseline frequencies of micronuclei (MN) in peripheral blood lymphocytes of human populations have been reported previously. Polymorphisms in a few metabolic enzyme genes seem to account for a proportion of this variability, but the impact of specific genetic variants on MN frequencies has not yet been clarified. In 42 healthy Japanese non-smoking men, we investigated the relationship between the MN frequency levels and genetic polymorphisms in three different genes: aldehyde dehydrogenase 2 (ALDH2), X-ray repair cross-complementing group 1 (XRCC1) and excision repair cross-complementing group 2 (ERCC2). Genotyping was performed by PCR–RFLP analysis. The ALDH2 variant (deficient-type) was significantly associated with increased MN frequency levels in subjects with drinking more than three times per week, whereas the XRCC1 and ERCC2 variants seemed to be unrelated to the MN frequency. The ALDH2-deficient habitual drinkers had an average MN frequency of 5.88 ± 0.58 (±S.E.) compared with 3.20 ± 0.80 in the ALDH2-proficient habitual drinkers (P< 0.05). The ALDH2-proficient non-habitual drinkers had the lowest MN frequency (1.56 ± 0.41). Furthermore, subjects with highest levels of mean MN frequency, who consumed more than 100g of alcohol per week and more than three times per week, had A2 genotype of ALDH2. A significant odds ratio (12.25, P< 0.05) for the MN frequency levels above the 50th percentile value was observed for the ALDH2-deficient individuals versus the ALDH2-proficient individuals after adjustment for several confounders. These results strongly suggest that human early genotoxic effect studies based on the cytogenetic markers of MN should take into account both the individual ALDH2 polymorphism and the potential confounding effect of the drinking behavior. © 2003 Elsevier B.V. All rights reserved. Keywords: ALDH2; Habitual drinker; Micronuclei Abbreviations: CAs, chromosomal aberrations; SCEs, sister chromatids exchanges; MN, micronuclei; ALDH2, aldehyde dehydrogenase 2; XRCC1, X-ray repair cross-complementing group 1; ERCC2, excision repair cross-complementing group 2; CB, cytokinesis-block; OR, odds ratio; CI, confidence interval; wk, week ∗ Corresponding author. Tel.: +81-59-231-5012; fax: +81-59-231-5012. E-mail address: jinishi@doc.medic.mie-u.ac.jp (H. Ishikawa). 1383-5718/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/S1383-5718(03)00179-7