Association of alcohol dehydrogenase 2*1 allele with liver damage and insulin concentration in the Japanese

Abstract

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 insulinglucose 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, c-GTP, and prevalence of diabetes were compared among the ADH2 genotypes. The percentage of drinkers, alcohol consumption, AST, ALT, and c-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.

Alcohol use and fasting glucose in a developing southern Chinese population: the Guangzhou Biobank Cohort Study

“…Alternatively, alcohol may be protective but possession of ALDH2*2 alleles could be associated with both lower blood glucose and a greater inclination to never-drinking. However, the limited evidence available does not suggest that this is the case 22 23…”

Regulation of cytochrome P450 2e1 expression by ethanol: role of oxidative stress-mediated pkc/jnk/sp1 pathway

“…5 However, alcohol-inducible CYP2E1 also has an important role in alcohol metabolism and mediate liver impairment among variety of alcohol drinkers. 2 Although the role of CYP2E1 in alcohol-mediated liver toxicity is well known, similar studies are limited in extra-hepatic cells, especially cells from the CNS.…”

Effects of alcohol abstinence on glucose metabolism in Japanese men with elevated fasting glucose: A pilot study

“…Indeed, the prevalence of ADH1B and ALDH2 of the subjects in this study was similar to those reported in Japanese population. It has been reported that differences in these polymorphic ethanol-metabolizing enzymes influence FPG level25, glycemic control26, insulin level27 and risk for diabetes28. Thus, we speculate that differences in the distribution of polymorphic ethanol-metabolizing enzymes between Asians and Caucasians may be responsible for the differences in the relation between alcohol intake and hepatic insulin sensitivity.…”