CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database
CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database
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DOI：
10.1038/tpj.2013.2
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发表时间：
2014-02-01
影响因子：
2.8
通讯作者：
Cai, J-P
中科院分区：
文献类型：
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作者：
Dai, D-P;Xu, R-A;Cai, J-P
CYP2C9基因多态性显着影响某些药物的药代动力学和药效学，可能导致药物不良反应和治疗失败。已经对中国汉族人群中的 CYP2C9 基因多态性进行了多项研究。然而，这些研究仅关注样本量相对较小的两个常见研究的等位基因*2 和*3。为了扩大基因扫描区域并确定中国人群遗传分布模式的相对精确数据，招募了来自浙江省（n - 1127）和河北省（n - 1000）的无血缘关系的健康汉族志愿者作为受试者，对 CYP2C9 所有外显子进行直接测序。结果，本工作检测到了14个先前报道的等位基因，其中8个等位基因（*14、*16、*19、*23、*27、*29、*33和*34）是首次在中国人群中描述。此外，还检测到37个新突变，其中22个变体是非同义的，21个新等位基因*36-*56由人类CYP等位基因命名委员会指定。对这 22 个新型 CYP2C9 变体的体外功能分析表明，17 个突变对该蛋白的催化活性具有显着影响。我们的研究提供了中国汉族人群中 CYP2C9 多态性的最准确数据，并检测到迄今为止存在的最大数量的新型等位基因变异。这些新的等位基因将极大地丰富目前对中国人群中自然发生的 CYP2C9 变异的了解。
Genetic polymorphisms of CYP2C9 significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies have been performed on CYP2C9 genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles, *2 and *3, in relatively small sample sizes. To scale up the gene-scanning region and determine relatively precise data on the genetic distribution pattern in Chinese populations, unrelated healthy Han Chinese volunteers from Zhejiang Province (n - 1127) and Hebei (n - 1000) Province were recruited as subjects for the direct sequencing of all exons of CYP2C9. As a result, 14 previously reported alleles were detected in this work, and 8 of these alleles (*14, *16, *19, *23, *27, *29, *33 and *34) were described for the first time in Chinese populations. In addition, 37 novel mutations were also detected, of which 22 variants were non-synonymous, and 21 new alleles, *36-*56, were designated by the Human CYP Allele Nomenclature Committee. In vitro functional analysis of these 22 novel CYP2C9 variants revealed that 17 mutations had a significant influence on the protein's catalytic activity. Our study provides the most accurate data on CYP2C9 polymorphisms in Han Chinese populations and detects the largest number of novel allelic variants existing to date. These new alleles will greatly enrich the current knowledge of naturally occurring CYP2C9 variants in Chinese populations.