Relation among alcohol dehydrogenase 2 polymorphism, alcohol consumption, and levels of gamma-glutamyltransferase

In human beings, alcohol is metabolized primarily by alcohol dehydrogenase 2 (ADH2) and acetaldehyde dehydrogenase 2 (ALDH2). Whereas polymorphisms of the ALDH2 are common in Asian persons, polymorphisms of the ADH2 seem to be more important in Caucasian individuals. The aim of this study was to assess the relation among ADH2 polymorphism, alcohol consumption, and levels of gamma-glutamyltransferase (GGT). The question was examined among 1,663 subjects (736 men and 927 women) participating in a national representative health and nutrition survey (VERA substudy of the German National Nutrition Survey). Alcohol consumption was assessed through responses to a semiquantitative food frequency questionnaire (FFQ), and the ADH2 restriction fragment length polymorphism (RFLP) Mae III and GGT levels were analyzed from frozen serum samples. The relations between the polymorphism and alcohol consumption and between alcohol consumption and GGT levels according to the polymorphism were assessed with the use of descriptive statistics and contingency table analysis. Of the subjects studied, 2.8% were homozygous or heterozygous for the ADH2*2 allele, and high levels of alcohol consumption (>20 g/day) were less common among these subjects (8.5%) than among subjects with the ADH2*1 allele (19.9%). Median levels of GGT increased with increasing levels of alcohol consumption. This increase tended to be stronger among subjects with the ADH2*2 allele than among other subjects, although differences were not statistically significant (P value for interaction=.1) given the small number of subjects with the polymorphism. These results are consistent with the hypothesis that subjects with the ADH2*2 allele, on the one hand, might tend to drink less alcohol but, on the other hand, might be at increased risk of alcohol-related effects on the liver with consumption of larger amounts of alcohol. However, this hypothesis needs to be evaluated among larger population samples.