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-4 5011E1 (CYP2E1) gene on ethanol elimination rate in alcoholic patients and healthy subjects. The CYP2E1 genotype was determined by polymeras e chain reaction-restriction fragment length polymorphism method for 1 24 alcoholics and 54 healthy subjects. There was no significant differ ence in the gene frequency of CYP2E1 between alcoholics and healthy co ntrol subjects. Blood ethanol concentrations in the 65 alcoholics on a dmission ranged from 0.32 to 4.22 mg/ml. In the patients with the c1/c 2 genotype, the elimination rate was significantly correlated with blo od ethanol concentration. In each of the three genotypes of CYP2E1, th e patients were divided into three groups based on ethanol concentrati ons. The average of the ethanol elimination rate in the patients with c1/c2 having blood ethanol levels of greater than or equal to 2.5 mg/m l was significantly higher than the rates in the two other groups of c 1/c2. When blood ethanol levels were greater than or equal to 2.5 mg/m l, the elimination rate in the patients with c1/c2 was significantly h igher than that in those with c1/c1. Regardless of the CYP2E1 genotype , the elimination rate in the alcoholics was higher than that in the c ontrol subjects when blood ethanol levels were <1.0 mg/ml. These resul ts suggest the possibility that the c2 allele of CYP2E1 influences the rate of ethanol elimination at high ethanol levels, The rate of ethan ol elimination was independent of liver disorder judged by serum total bilirubin values.