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

J Hepatol. 2004 Nov;41(5):744-50. doi: 10.1016/j.jhep.2003.06.003.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Dehydrogenase / genetics*
  • Alcoholism / genetics*
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Cytochrome P-450 CYP2E1 / genetics*
  • Gene Frequency
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Liver Diseases, Alcoholic / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Spain

Substances

  • ADH1B protein, human
  • ADH1C protein, human
  • Alcohol Dehydrogenase
  • Cytochrome P-450 CYP2E1
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial