三维凝胶基因芯片法研究中国人群CYP2C9与CYP2C19基因多态性

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (9): 966-973.

三维凝胶基因芯片法研究中国人群CYP2C9与CYP2C19基因多态性

马晶晶¹, 李金恒¹, 程璐²

¹南京大学医学院临床学院, 南京军区南京总医院药理科, 南京210002, 江苏;
²东南大学国家生物电子学重点实验室, 南京210009, 江苏

收稿日期:2009-05-12 修回日期:2009-08-04 发布日期:2020-11-03
通讯作者: 李金恒, 男, 博士, 教授, 博士生导师, 研究方向:临床药理学。Tel:025-80863098 E-mail: ljhengyr@jlonline.com
作者简介:马晶晶, 女, 硕士研究生, 研究方向:临床药理学。Tel:15850560332 E-mail: jasmine526@hotmail.com
基金资助:
国家自然科学基金资助项目(No30472055)

Study on the CYP2C9 and CYP2C19 genetic polymorphism in Chinese subjects by using 3-dimense polyacrylamide gel-based microarray platform

MA Jing-jing¹, LI Jin-heng¹, CHENG Lu²

¹Department on Pharmacology, School ofMedicine, NanjingUniversity, Nanjing General Hospital of Nanjing Military Command, PLA, Nanjing 210002, Jiangsu, China;
²StateKey Laboratory of Bioelectronics, Southeast University, Nanjing 210009, Jiangsu, China

Received:2009-05-12 Revised:2009-08-04 Published:2020-11-03

摘要/Abstract

摘要： 目的: 应用三维凝胶基因芯片方法研究中国人群CYP2C9 与CYP2C19 基因多态性, 为临床合理用药提供新的技术手段与研究方法。方法: 提取207 名男性健康志愿者基因组DNA, PCR 分别扩增包含CYP2C9^*3 、^*13 与CYP2C19^*2 、^*3 多态位点目标片段, 制备三维凝胶基因芯片, 荧光标记探针杂交, 芯片扫描并基因分型, 用直接测序法对结果进行验证。结果: 207 人中, 11 人为CYP2C9^*1/^*3 基因型, 1 人为CYP2C9^*1/^*13 基因型, 1 人为CYP2C9^*3/^*3 基因型。2C9^*3 、^*13等位基因发生率分别为2.90 %、0.24 %, 慢代谢型发生率为0.48 %。CYP2C19 突变杂合子有97人, 突变纯合子有26 人, 2C19^*2 、^*3 等位基因发生率分别为32.85 %、3.62 %, 慢代谢型发生率为12.56 %。四种等位基因型分布均符合Hardy-Weinberg 平衡。结论: 三维凝胶基因芯片方法可为临床快速基因分型提供高效平台。CYP2C9 与CYP2C19 基因在中国人群存在普遍多态性, 检测其基因型可有效指导相关临床治疗药物应用, 提高药效, 降低不良反应。

关键词: CYP2C9, CYP2C19, 基因多态性, 三维凝胶基因芯片, DNA 纯化

Abstract: AIM: To study the genetic polymorphisms of CYP2C9 and CYP2C19 by using 3-dimense polyacrylamide gel-based microarray method in healthy male Chinese subjects, providing original technology and research method for clinical rational administration. METHODS: 207 healthy male Chinese volunteers were recruited and their genomic DNA were isolated. The genomic fragments containing CYP2C9 ^* 3, ^* 13 and CYP2C19 ^* 2, ^* 3 polymorphic sites were amplified respectively to prepare 3-dimense polyacrylamide gel-based microarrays. After hybridized by fluorescent labeling probes, the microarrays were scanned to obtain genotyping results of CYP2C9 and CYP2C19.The analytic results were confirmed by direct sequencing. RESULTS: In 207 volunteers, the number of subjects with CYP2C9 ^* 1/^*3, CYP2C9 ^* 1/^* 13 and CYP2C9 ^* 3/^* 3 genotype were 11, 1, and 1, respectively. The frequencies of CYP2C9 ^* 3 and CYP2C9 ^* 13 alleles were 2.90 %and 0.24 %, respectively. The incidence of CYP2C9 poor metabolizers was 0.48 %. With regard to CYP2C19, heterozygous variants were 97 and homozygous variants were 26.The frequencies of CYP2C19 ^* 2 and CYP2C19 ^* 3 alleles were 32.85 % and 3.62 %, respectively. The incidence of CYP2C19 poor metabolizers was 12.56 %.The distribution of the four alleles were all coincident with Hardy-Weinberg law. CONCLUSION: 3-dimense polyacrylamide gelbased microarray method could serve as an advanced platform for clinical genotyping. The polymorphisms of CYP2C9 and CYP2C19 are frequent in Chinese population. Detecting the Genotyping CYP2C9 and CYP2C19 gene before administration could optimize related clinical drugs therapy, with the purpose of high efficiency and low incidence of adverse reactions.

Key words: CYP2C9, CYP2C19, genetic polymorphism, 3-dimense polyacrylamide gel-based microarray, DNA purification

中图分类号:

R969

马晶晶, 李金恒, 程璐. 三维凝胶基因芯片法研究中国人群CYP2C9与CYP2C19基因多态性[J]. 中国临床药理学与治疗学, 2009, 14(9): 966-973.

MA Jing-jing, LI Jin-heng, CHENG Lu. Study on the CYP2C9 and CYP2C19 genetic polymorphism in Chinese subjects by using 3-dimense polyacrylamide gel-based microarray platform[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(9): 966-973.

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