Genetic variations of S-mephenytoin 4'-hydroxylase (CYP2C19) in the Chinese population.

Most of phenotyping studies have shown that Chinese populations have a higher incidence of poor metabolizers (PMs) of S-mephenytoin 4'-hydroxylation compared with populations of African and European descent. The present study was aimed at defining an exact population frequency of the genetic defect of S-mephenytoin 4'-hydroxylase (CYP2C19) in native and overseas Chinese healthy populations. All the related data were systematically summarized and re-analyzed using meta-analysis method, and consistency between phenotypic and genotypic frequencies of the PM was tested. A statistically significant homogeneity was across all 11 phenotyping studies (chi2 = 15.17, d.f. = 10; P > 0.05) and also across the remaining 4 genotyping studies (chi2 = 2.61, d.f. = 3; P > 0.05) except for a non-randomly selected population analysis. An approximate estimate of the PM phenotypic and genotypic frequencies was 13.6% (212 of 1555; 95% CI: 11.9%-15.3%) and 13.8% (79 of 573; 95%CI: 11.0%-16.6%), respectively. There was a good consistency between phenotyped and genotyped PM frequencies. The half of all genotyped EMs (50.3%, 276 of 549) were heterozygotes. The data estimate that 14% of Chinese would be homozygotes of CYP2C19 defective alleles, and that 176 million Chinese would be slow metabolizers of CYP2C19 substrates.