Xie H G
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Life Sci. 2000 Feb 25;66(14):PL175-81. doi: 10.1016/s0024-3205(00)00446-x.
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.
大多数表型研究表明，与非洲和欧洲血统的人群相比，中国人群中S-美芬妥因4'-羟化代谢不良者（PMs）的发生率更高。本研究旨在确定中国本土和海外健康人群中S-美芬妥因4'-羟化酶（CYP2C19）基因缺陷的确切人群频率。使用荟萃分析方法对所有相关数据进行系统总结和重新分析，并测试PM表型频率和基因型频率之间的一致性。除了一项非随机选择的人群分析外，所有11项表型研究（χ2 = 15.17，自由度 = 10；P > 0.05）以及其余4项基因分型研究（χ2 = 2.61，自由度 = 3；P > 0.05）均具有统计学意义上的同质性。PM表型频率和基因型频率的近似估计分别为13.6%（1555例中的212例；95%可信区间：11.9%-15.3%）和13.8%（573例中的79例；95%可信区间：11.0%-16.6%）。表型和基因型PM频率之间具有良好的一致性。所有基因分型的快代谢者（EMs）中有一半（50.3%，549例中的276例）为杂合子。数据估计，14%的中国人将是CYP2C19缺陷等位基因的纯合子，并且1.76亿中国人将是CYP2C19底物的慢代谢者。
