DEBRISOQUINE AND S-MEPHENYTOIN HYDROXYLATION PHENOTYPES AND GENOTYPESIN A KOREAN POPULATION

One hundred and fifty-two healthy Korean volunteers were phenotyped wi th debrisoquine and mephenytoin and genotyped with respect to CYP2D6. The debrisoquine metabolic ratio (MR) varied between 0.09 and 6.3, and all subjects were thus classified as extensive metabolizers of debris oquine. Polymerase chain reaction (PCR)-based amplification of genomic DNA with primers specific for the C-188-->T mutation present in exon 1 of the CYP2D610B allele was performed and revealed an allele freque ncy of 0.51 in this Korean population. Forty-three subjects (28%) were homozygous for CYP2D610B, 69 subjects (45%) were heterozygous for th is allele, while in 40 subjects (26%) no exon 1 mutation could be foun d. All subjects except one homozygous for the wild type allele had MRs below 0.75 whereas the MR was higher than 0.99 in all subjects homozy gous for the CYP2D610B allele. The MRs in the three genotype groups w ere significantly different (p <0.0001; Kruskal-Wallis test). Eco RI R FLP analysis of DNA from six subjects with debrisoquine MRs less than or equal to 0.11 revealed that only one (MR 0.09) carried a duplicated CYP2D62-gene (CYP2D6*2X2) as indicated by the Eco RI 12.1 kb haploty pe. It is concluded that, as shown earlier for Chinese and Japanese po pulations, the CYP2D610B-allele containing the C-188-->T mutation is the major cause of diminished CYP2D6 activity in Koreans. In this Kore an population, the MR of debrisoquine was shifted towards higher value s (lower CYP2D6 activity) compared with Caucasian populations but the shift appeared to be less pronounced than earlier shown for Chinese. T wenty-four subjects (16%) were poor metabolizers of S-mephenytoin as i ndicated by the SIR mephenytoin ratio of about 1. Twenty-three of thes e were genotyped with respect to the defect CYP2C19-alleles CYP2C192 and CYP2C193. Of the 46 poor metabolizer alleles, 32 (70%) were CYP2C 192 and the remaining 14 (30%) were CYP2C19*3. Thus, the defect CYP2C 192 and CYP2C19*3-alleles explained 100% of the 23 Korean poor metabo lizers of S-mephenytoin.