Effect of the cytochrome P-450IIE1 genotype on ethanol elimination rate in alcoholics and control subjects.
We studied an influence of genetic polymorphisms in the cytochrome P-450IIE1 (CYP2E1) gene on ethanol elimination rate in alcoholic patients and healthy subjects. The CYP2E1 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method for 124 alcoholics and 54 healthy subjects. There was no significant difference in the gene frequency of CYP2E1 between alcoholics and healthy control subjects. Blood ethanol concentrations in the 65 alcoholics on admission ranged from 0.32 to 4.22 mg/ml. In the patients with the c1/c2 genotype, the elimination rate was significantly correlated with blood ethanol concentration. In each of the three genotypes of CYP2E1, the patients were divided into three groups based on ethanol concentrations. The average of the ethanol elimination rate in the patients with c1/c2 having blood ethanol levels of > or = 2.5 mg/ml was significantly higher than the rates in the two other groups of c1/c2. When blood ethanol levels were > or = 2.5 mg/ml, the elimination rate in the patients with c1/c2 was significantly higher than that in those with c1/c1. Regardless of the CYP2E1 genotype, the elimination rate in the alcoholics was higher than that in the control subjects when blood ethanol levels were < 1.0 mg/ml. These results suggest the possibility that the c2 allele of CYP2E1 Influences the rate of ethanol elimination at high ethanol levels. The rate of ethanol elimination was independent of liver disorder judged by serum total bilirubin values.
Ueno
Y
Y
Department of Legal Medicine, Kobe University School of Medicine, Japan.
Adachi
J
J
Imamichi
H
H
Nishimura
A
A
Tatsuno
Y
Y
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000097:blood / Q000235:genetics*; D000483:Alleles; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics
D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating