GENETIC-POLYMORPHISM OF CYTOCHROME P4502E1 AND RISK OF ALCOHOLIC LIVER-DISEASE IN CAUCASIANS

Genetic factors may be of importance in determining inter-individual s usceptibility to alcoholic liver disease (ALD), Among the candidate ge nes which have been considered to be important are those which code fo r enzymes involved in alcohol metabolism, Cytochrome P4502E1 (CYP2E1) metabolizes alcohol to acetaldehyde and the hydroxyethyl radical, and is also inducible by alcohol, A Rsa I restriction fragment length poly morphism (RFLP) in the 5'-flanking region of the CYP2E1 gene has been identified by other investigators, studies showing that the mutant all ele (termed c(2)) shows greater transcriptional activity, higher prote in levels and increased activity compared with the wild-type allele (c (1)), We have used PCR-RFLP analysis to determine whether the frequenc y of these alleles differed in 95 Caucasian patients with ALD compared with 205 control subjects (comprising 58 alcoholics with no liver dis ease, 47 patients with non-alcoholic liver disease and 100 healthy vol unteers), In controls, the frequency (0.024) of the c(2) allele was si milar to that previously reported in other Caucasian populations. The c(2) allele frequency in patients with ALD (0.1), however, was signifi cantly (p = 0.0003; odds ratio (OR) 4.5, 95% CI 1.9-10.9) higher than in control subjects, The findings indicate that Caucasians carrying th e Rsa I c(2) allele of the CYP2E1 gene may be at higher risk of develo ping ALD if they abuse alcohol.