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

Most of phenotyping studies have shown that Chinese populations have a high er incidence of poor metabolizers (PMs) of S-mephenytoin 4'-hydroxylation c ompared 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 he althy populations. All the related data were systematically summarized and re-analyzed using metaanalysis method, and consistency between phenotypic a nd genotypic frequencies of the PM was tested. A statistically significant homogeneity was across all 11 phenotyping studies (X-2 = 15.17, d.f. = 10; P > 0.05) and also across the remaining 4 genotyping studies (X-2 = 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 hom ozygotes of CYP2C19 defective alleles, and that 176 million Chinese would b e slow metabolizers of CYP2C19 substrates. (C) 2000 Elsevier Science Inc.