title: Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele.
abstract: The incidence of the S-mephenytoin polymorphism was compared in two Chinese ethnic groups, Han (n = 101) and Bai (n = 202) by phenotype and genotype analysis. The frequency of poor metabolizers (PMs) in Han vs. Bai subjects was 19.8% vs. 13.4%. Han subjects had a higher frequency of the mutant CYP2C19m1 allele (0.366 vs. 0.257, P < .01) and a lower frequency of the wild-type allele (0.559 vs. 0.688, P < .01) than Bai subjects, which is consistent with the difference in the frequencies of PMs between the two ethnic groups. This results in a lower percentage of homozygous wild-type extensive metabolizers of mephenytoin (EMs) in Han subjects than in Bai subjects (40% vs. 59%, P = .005). Therefore, Han subjects may be more susceptible than Bai subjects to the drugs metabolized by the CYP2C19 enzyme. Ratios of urinary S/R-mephenytoin in homozygous EMs were lower than those of heterozygous EMs for both Han and Bai subjects, which shows a gene-dosage effect. Genotype analysis identified all but one PM as homozygous or heterozygous for the two known mutant CYP2C19m1 and/or CYP2C19m2 alleles. A single Bai PM outlier was shown to be heterozygous for CYP2C19m1 and a new mutant CYP2C19 allele containing a single amino acid change of Arg433 --> Trp433. A genotyping test demonstrated that only this one individual carried this rare allele (frequency of 0.0025 in Bai subjects).
authors.affiliation: Pharmacogenetics Research Institute, Hunan Medical University, Changsha, People's Republic of China.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Xiao
authors.forename: J A
authors.initials: JA
authors.lastname: Goldstein
authors.forename: H G
authors.initials: HG
authors.lastname: Xie
authors.forename: J
authors.initials: J
authors.lastname: Blaisdell
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: C H
authors.initials: CH
authors.lastname: Jiang
authors.forename: F X
authors.initials: FX
authors.lastname: Yan
authors.forename: N
authors.initials: N
authors.lastname: He
authors.forename: S L
authors.initials: SL
authors.lastname: Huang
authors.forename: Z H
authors.initials: ZH
authors.lastname: Xu
authors.forename: H H
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D002681:China / Q000208:ethnology; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19