Genetic variations of human CYP2D6 in the Chinese Han population
Genetic variations of human CYP2D6 in the Chinese Han population
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DOI：
10.2217/pgs.13.160
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发表时间：
2013-11-01
期刊：
影响因子：
2.1
通讯作者：
Cai, Jian-Ping
中科院分区：
文献类型：
--
作者：
Qian, Jian-Chang;Xu, Xin-Min;Cai, Jian-Ping
目的：本研究的目的是检测中国汉族人群CYP 2D 6基因的遗传多态性，并阐明其等位基因的分布模式。材料和方法：我们使用PCR和双向测序方法分析了来自中国两个地理位置（北方和南方地区）的2129名无关健康中国汉族受试者的CYP 2D 6基因的所有9个外显子。结果：在2129名受试者中共检测到165个突变位点，其中67个位点为首次报道。在这些新的突变位点中，22个为非同义突变，12个被人类等位基因命名委员会命名为新的等位基因（*87-*93，* 94 A，* 94 B和 *95-*98）。此外，在1954名志愿者中还检测到29种已报道的等位基因和84种基因型。新变体的功能预测显示，8个变体可能对CYP 2D 6产生有害影响。分别进行连锁不平衡分析和tagSNP选择。通过使用这些方法，发现两个地区之间存在明显差异。结论：这项研究提供了迄今为止中国汉族人群中最全面的CYP 2D 6多态性数据，并增加了已知等位基因的数量;这些发现可能极大地有助于中国汉族人群个体化药物的开发。原件提交日期：2013年1月1日;修订日期：2013年8月14日
Aim: The purpose of this study was to determine the genetic polymorphisms of the CYP2D6 gene and to elucidate the allele distribution pattern in the Chinese Han population. Materials & methods: We used PCR and bidirectional sequencing methods to analyze all nine exons of the CYP2D6 gene in 2129 unrelated, healthy Chinese Han subjects from two geographical locations in China: the northern and southern regions. Results: In total, 165 mutated sites were detected in 2129 participants, of which 67 sites were reported for the first time. Among these novel mutation sites, 22 were nonsynonymous and 12 were named as novel alleles (*87-*93, *94A, *94B and *95-*98) by the Human CYP Allele Nomenclature Committee. In addition, 29 previously reported alleles and 84 genotypes were also detected in 1954 volunteers. Functional prediction of novel variants revealed that eight variants might have a deleterious effect on CYP2D6. Linkage disequilibrium analysis and tagSNP selection were performed separately. By using these methods, distinct differences were found between the two regions. Conclusion: This study provides the most comprehensive data concerning CYP2D6 polymorphisms in the Chinese Han population to date and increases the number of known alleles; these findings may greatly contribute to the development of personalized medicine for the Chinese Han population. Original submitted 1 January 2013; Revision submitted 14 August 2013