Association of alcohol dehydrogenase 2*1 allele with liver damage and insulin concentration in the Japanese.
The Japanese have a polymorphism in the alcohol dehydrogenase 2 gene (ADH2). The alleles of ADH2 (ADH2*1 and ADH2*2) encode more active and less active forms for ethanol metabolism, respectively. We examined whether liver damage and the insulin-glucose axis vary according to ADH2 genotype in the Japanese. The 2,232 subjects (1,126 men and 1,106 women) were recruited from a population-based prospective cohort study. Clinical evaluations including alcohol consumption, percentage of alcohol drinkers, plasma glucose, HbA1c, insulin, AST, ALT, gamma-GTP, and prevalence of diabetes were compared among the ADH2 genotypes. The percentage of drinkers, alcohol consumption, AST, ALT, and gamma-GTP were higher in group ADH2*1/1 than in group ADH2*1/2 or ADH2*2/2 (all P < 0.05). Hence, ADH2*1/1 is associated with excess alcohol intake and liver disorders. However, the prevalence of diabetes did not differ among the three groups. For the glucose-insulin axis, we examined subjects who did not receive insulin therapy or oral anti-diabetes medication. While amounts of alcohol consumed and glucose levels were nearly the same between ADH*1/2 and ADH2*2/2, insulin concentrations were lower in ADH2*2/1 than in ADH2*2/2 (P < 0.05 in men). This finding suggests that the ADH2*1 allele is associated with a lower insulin concentration when alcohol intake is light or moderate. It also suggests that the genetic effect of ADH2*1 plays an important role in alcohol drinking behavior and in the occurrence of liver injury, but the effect is so mild that it does not influence the glucose-insulin axis or prevalence of diabetes.
Suzuki
Yoshihiko
Y
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan. dr-suzuki@nifty.com.|Hokendohjin Medical Foundation, Tokyo, Japan. dr-suzuki@nifty.com.
Ando
Fujiko
F
Department of Epidemiology, National Institute for Longevity Sciences, Obu, Aichi 474-8522, Japan.
Ohsawa
Ikuroh
I
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan.
Shimokata
Hiroshi
H
Department of Epidemiology, National Institute for Longevity Sciences, Obu, Aichi 474-8522, Japan.
Ohta
Shigeo
S
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan.
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood*; D007564:Japan; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D007328:Insulin; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase