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中国循证儿科杂志

中国循证儿科杂志 ›› 2016, Vol. 11 ›› Issue (1): 34-37.

• 论著 • 上一篇    下一篇

儿童华法林药动和药效相关基因型频率和通路富集研究

杨琳1 董辰1 王慧君 卢宇蓝周 文浩   

  1. 复旦大学附属儿科医院分子诊断中心 上海，201102; 1 共同第一作者
  • 收稿日期:2016-02-23 修回日期:2016-02-23 出版日期:2016-02-05 发布日期:2016-02-05
  • 通讯作者: 卢宇蓝 周文浩

Study on the enrichment of warfarin genotype frequency and pathway associated with its pharmacokinetics and drug effect in children

YANG Lin1, DONG Chen1, WANG Hui-jun, LU Yu-lan, ZHOU Wen-hao   

  1. Children's Hospital of Fudan University, Shanghai 201102, China; 1 Co-first author
  • Received:2016-02-23 Revised:2016-02-23 Online:2016-02-05 Published:2016-02-05
  • Contact: LU Yu-lan, ZHOU Wen-hao

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摘要：

目的 探讨华法林药动和药效相关基因位点的人群频率差异，为华法林药物基因组学研究提供基础数据。方法 利用复旦大学附属儿科医院(我院)620例全外显子测序（WES）数据，对公共数据库中已报道的华法林药物相关位点计算等位基因频率。与千人基因组东亚人和欧洲人的等位基因频率进行比较。结果 我院620例WES数据共检测到27个药物相关的多态性位点，涉及12个基因。27个华法林药物相关位点中，3个位点在这3组人群间差异无统计学意义（P≥0.01）； 10个位点在我院WES数据与千人基因组东亚人等位基因频率差异无统计学意义（P≥0.01）、与千人基因组欧洲人等位基因频率差异有统计学意义（P<0.01）；1个位点我院WES数据与千人基因组东亚人等位基因频率差异有统计学意义(P<0.01)、与千人基因组欧洲人等位基因频率差异无统计学意义（P≥0.01）；13个位点在我院WES数据与千人基因组东亚人、欧洲人等位基因频率差异均有统计学意义（P<0.01）。结论 华法林已报道的药物相关位点存在明显种族差异性，明确其变异为制定华法林个体化给药的精准医疗提供了基础数据。

Abstract:

Objective The study of pharmacogenomics focused on how mutations of essential enzyme genes would lead to different drug response. It would be of great importance to identify warfarin-response-related variants of the patients before clinical treatment, especially for pediatrics.Methods In this study, the allele frequencies of reported clinically significant warfarin-response-related variants were evaluated based on 620 WES data collected from Children Hospital of Fudan University. Then the local allele frequencies were compared with public population-based databases, including 1000 Genomes project.Results 27 warfarin-response-related variants that have clinical significance were detected in the 620 WES data that we used. These variants were distributed in 12 genes. There were 27 warfarin-related variants, and the frequency of 3 variants in our data showed no difference with European and East Asian population of 1000 Genome project（P≥0.01）, 10 of them showed no difference with East Asian （P≥0.01） but were significantly different from European population （P<0.01）, 1 variant showed no difference with European and different fromh East Asian（P≥0.01）, and 13 variants were different from both population frequency data（P<0.01）.Conclusion Warfarin-response-related variants detected in our database also show population-specificity, which indicates that sufficient genome-wide data preparation are necessary for the personized drug usage and the practice of precise medicine.