GENETIC-ANALYSIS OF THE S-MEPHENYTOIN POLYMORPHISM IN A CHINESE POPULATION

The 4'-hydroxylation of S-mephenytoin exhibits a polymorphism in human s, with the poor metabolizer phenotype exhibiting a lower frequency in white (3% to 5%) than in Oriental populations (13% to 23%). Two mutat ions in CYP2C19 (CYP2C19(m1) and CYP2C19(m2) have recently been descri bed that account for similar to 85% of white and 100% of Japanese poor metabolizers. This study examines whether these mutations account for the poor metabolizer phenotype in the Chinese population. The metabol ism of S-mephenytoin exhibited a bimodal distribution in 244 unrelated Chinese subjects, although the distribution of the two phenotypes ove rlapped. In 75 selected Chinese subjects, CYP2C19 genotype analysis pr edicted the phenotype with 100% accuracy. The frequency of the poor me tabolizer phenotype was similar to 11% (95% confidence interval 7% to 15%). The frequency of the CYP2C19(m1) allele was 0.289, whereas that of CYP2C19(m2) was 0.044. Homozygous extensive metabolizers had slight ly lower ratios of S/R-mephenytoin compared with heterozygous extensiv e metabolizers, showing a gene-dosage effect. These data show the adva ntages of genotype analysis in investigations of the mephenytoin pheno type in Oriental subjects.