PT - JOURNAL ARTICLE AU - Zhou-Sheng Xiao AU - Joyce A. Goldstein AU - Hong-Guang Xie AU - Joyce Blaisdell AU - Wei Wang AU - Chang-Hong Jiang AU - Feng-Xiang Yan AU - Nan He AU - Song-Ling Huang AU - Zhen-Hua Xu AU - Hong-Hao Zhou TI - Differences in the Incidence of the <em>CYP2C19</em>Polymorphism Affecting the <em>S</em>-Mephenytoin Phenotype in Chinese Han and Bai Populations and Identification of a New Rare<em>CYP2C19</em> Mutant Allele DP - 1997 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 604--609 VI - 281 IP - 1 4099 - http://jpet.aspetjournals.org/content/281/1/604.short 4100 - http://jpet.aspetjournals.org/content/281/1/604.full SO - J Pharmacol Exp Ther1997 Apr 01; 281 AB - 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 (0.366vs. 0.257, P &lt; .01) and a lower frequency of the wild-type allele (0.559 vs. 0.688, P &lt; .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 mutantCYP2C19m1 and/orCYP2C19m2 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). The American Society for Pharmacology and Experimental Therapeutics