CYTOCHROME-P450 2E1 GENOTYPE AND CHLORZOXAZONE METABOLISM IN HEALTHY AND ALCOHOLIC CAUCASIAN SUBJECTS

Susceptibility to cancer or ethanol-related liver diseases may be asso ciated with a large variability in cytochrome P450 2E1 activity, This variability may be of genetic origin or reflect environmental factors, To test the role of genetics, the phenotype and genotype of this enzy me were determined in 42 non-alcoholic and 74 alcoholic patients hospi talized for detoxification treatment, Chlorzoxazone metabolism was use d to assess CYP2E1 phenotype, Restriction length fragment polymorphism s with Rsa I or Pst I, and Dra I endonucleases were used to determine the two mutant alleles, Pst I/Rsa I-c2 and Dra I-C. A significant gend er difference in basal CYP2E1 activity was observed in non-smoking con trols (p < 0.05) but not in alcoholics or smokers, Subjects heterozygo us for the C or c2 mutated allele did not show any difference in CYP2E 1 activity at the basal level, compared with the wild type homozygotes . Conversely, patients with the mutated genotype appeared less inducib le than the others after ethanol induction (p < 0.01).