Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic Caucasian subjects.
Susceptibility to cancer or ethanol-related liver diseases may be associated 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 enzyme were determined in 42 non-alcoholic and 74 alcoholic patients hospitalized for detoxification treatment. Chlorzoxazone metabolism was used to assess CYP2E1 phenotype. Restriction length fragment polymorphisms 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 gender difference in basal CYP2E1 activity was observed in non-smoking controls (p < 0.05) but not in alcoholics or smokers. Subjects heterozygous for the C or c2 mutated allele did not show any difference in CYP2E1 activity at the basal level, compared with the wild type homozygotes. Conversely, patients with the mutated genotype appeared less inducible than the others after ethanol induction (p < 0.01).
Lucas
D
D
Faculté de Médecine de Brest, Laboratoire de Biochimie-Nutrition, France.
Ménez
C
C
Girre
C
C
Berthou
F
F
Bodénez
P
P
Joannet
I
I
Hispard
E
E
Bardou
L G
LG
Ménez
J F
JF
D000328:Adult; D000437:Alcoholism / Q000201:enzymology*; D002753:Chlorzoxazone / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D012907:Smoking; D044465:White People / Q000235:genetics
D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases; C035594:TTTAAA -specific type II deoxyribonucleases; D002753:Chlorzoxazone