Association Between Gamma-Glutamyltranspeptidase Levels and Genetic Polymorphisms of Alcohol-Metabolizing Enzymes in Japanese Population

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  • Taki Kentaro
    Department of Clinical Preventive Medicine, Nagoya University Hospital
  • Nishio Kazuko
    Department of Preventive Medicine/ Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine.
  • Nakamura Sakurako
    Department of Clinical Preventive Medicine, Nagoya University Hospital
  • Sekido Yoshitaka
    Department of Clinical Preventive Medicine, Nagoya University Hospital
  • Hamajima Nobuyuki
    Department of Preventive Medicine/ Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine.
  • Niwa Toshimitsu
    Department of Clinical Preventive Medicine, Nagoya University Hospital

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Background Genetic variations in alcohol dehydrogenase 2 (ADH2) enzyme and aldehyde dehydrogenase 2(ALDH2) enzyme are associated with an aversion to alcohol and a lower risk of alcoholism in Japanese population. The aim of this study was to assess the relationship between gamma-glutamyltranspeptidase (GGT) levels and polymorphisms of ADH2 and ALDH2.<br>Methods This study included 476 Japanese taking medical check-up at Nagoya University Hospital. Alcohol intake was assessed through responses to a semiquantitative food frequency questionnaire. Genotypes of ADH2 His47Arg and ALDH2 GIu487Lys were determined by a duplex polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. Results Polymorphism of ADH2 His47Arg did not affect serum GGT levels. However, alcohol consumption affected GGT levels. In ADH2 47His/His and His/Arg genotypes, subjects with an alcohol intake of >20 g/day showed significantly higher GGT levels than those with 0 g/day. In contrast to ADH2, polymorphism of ALDH2 Glu487Lys significantly affected GGT levels in Japanese men. Male subjects with ALDH2 487Glu/Glu genotypes showed significantly higher GGT levels than those with Lys/Lys genotype. In ALDH2 487Glu/Gluand Glu/Lvs genotypes, subjects with an alcohol intake of>20 g/day showed significantly higher GGT levels than those with 0 g/day. Notably, male subjects with ALDH2 487Glu/Glu genotype showed a significantly increased risk for high GGT levels compared with Lys/Lys genotype. Conclusions Polymorphism of ALDH2 Glu487Lys affected GGT levels in Japanese men. Especially, those with ALDH2 487Glu/Glu genotype showed an increased risk for high GGT levels in Japanese men, because of their tendency to high alcohol consumption, although they are considered to have strong tolerance to alcohol.

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