Genetic polymorphisms of ADH2, ADH3, CYP4502E1 Dra-I and Pst-I, and ALDH2 in Spanish men: lack of association with alcoholism and alcoholic liver disease.
BACKGROUND/AIMS: The relationship between polymorphisms at the alcohol dehydrogenase 2 (ADH(2)), ADH(3), CYP(450)2E1 and aldehyde dehydrogenase 2 (ALDH(2)) loci and the individual predisposition to alcoholism and alcoholic liver disease in Caucasians is controversial. METHODS: We determined the genotypes of ADH(2), ADH(3), CYP(450)2E1 (Pst-I and Dra-I) and ALDH(2) in 519 male Spaniards: 264 alcoholic subjects (47 without liver disease, 118 with non-cirrhotic liver disease and 99 with cirrhosis) and 255 non-alcoholic subjects (64 healthy controls, 110 with non-cirrhotic non-alcoholic liver disease and 81 with cirrhosis unrelated to alcohol). Genotyping was performed using PCR-RFLP methods on white cell DNA. RESULTS: The distribution of the allelic variants (allele *1 and allele *2) in the whole subjects analyzed was: ADH(2) 93.1% and 6.9%; ADH(3) 55.7 and 44.3%; CYP(450)2E1 Dra-I 11.2 and 88.8%; CYP(450)2E1 Pst-I 96.2 and 3.8% and ALDH2 100 and 0%, respectively. No differences were observed in the allelic distributions of the alcoholic and non-alcoholic subjects for the loci examined. Allele distribution in alcoholics with no liver disease, with alcoholic steatosis or hepatitis, and with cirrhosis was also similar. CONCLUSIONS: ADH(2), ADH(3), and CYP(450)2E1 Pst-I and Dra-I genetic variations are not related to alcoholism or susceptibility to alcoholic liver disease in our male population. ALDH(2) locus is monomorphic.