title: Polymorphism in the cytochrome P450 2E1 gene and the risk of alcoholic liver disease.
abstract: OBJECTIVE
  To study the genetic susceptibility to alcoholic liver disease, we investigated the association between genetic polymorphism in the cytochrome P450 2E1 gene and the occurrence of alcoholic liver disease.
  
  
  METHODS
  Four previously described restriction fragment length polymorphisms (RFLPs) in the cytochrome P 450 2E1 gene were analyzed by restriction endonuclease (Dra I, Msp I, Pst I and Rsa I) digestion of polymerase chain reaction amplified DNA segments. Polymorphisms in these loci were compared to the occurrence of fatty liver, alcoholic hepatitis and liver fibrosis in 319 males comprising total abstainers, moderate alcohol consumers and chronic alcoholics.
  
  
  RESULTS
  The allelic frequencies for each RFLP in this series were: 0.89 and 0.11 (Dra I), 0.98 and 0.02 (Msp I) and 0.99 and 0.01 (Pst I and Rsa I). The distribution of the alleles did not vary significantly between the different consumption groups. The allelic frequencies among patients with fatty liver, alcoholic hepatitis or liver fibrosis were not significantly different from the allelic frequencies among patients with normal liver histology. Comparison of different genotypes among moderate alcohol consumers (n = 43) or chronic alcoholics (n = 243) with or without liver disease showed no statistically significant associations. However, the rare polymorphic (d2) allele in the Dra I RFLP was found slightly more often among moderate consumers as well as alcoholics with alcoholic liver disease.
  
  
  CONCLUSIONS
  These results indicate that the Msp I, Pst I and Rsa I RFLPs were very rare in the Finnish population, suggesting at most minor contribution to the inherited susceptibility to alcoholic liver disease. Polymorphism in the Dra I locus was more common in this study population, but showed no statistically significant association with alcoholic liver disease.
authors.affiliation: Department of Forensic Medicine, University of Helsinki, Finland. Vesa_Savolainen@fimug.fi
authors.forename: V T
authors.initials: VT
authors.lastname: Savolainen
authors.forename: J
authors.initials: J
authors.lastname: Pajarinen
authors.forename: M
authors.initials: M
authors.lastname: Perola
authors.forename: A
authors.initials: A
authors.lastname: Penttilä
authors.forename: P J
authors.initials: PJ
authors.lastname: Karhunen
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002874:Chromosome Mapping; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005235:Fatty Liver, Alcoholic / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006519:Hepatitis, Alcoholic / Q000235:genetics*; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
chemical_list: D019392:Cytochrome P-450 CYP2E1