中国2 型糖尿病人中CYP2C8 、CYP2C9 基因多态性

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (3): 300-306.

中国2 型糖尿病人中CYP2C8 、CYP2C9 基因多态性

何君^1,2, 周巍^1,3, 王练词¹, 何婷晔¹, 王丹¹, 范岚¹, 张伟¹, 周宏灏¹

¹中南大学临床药理研究所, 长沙410078, 湖南;
²中国医学科学院实验动物研究所新药安全评价研究中心, 北京100020;
³上海市公共卫生临床中心, 上海201508

收稿日期:2009-02-05 修回日期:2009-02-05 发布日期:2020-10-27
通讯作者: 周宏灏,, 男, 教授, 博士生导师, 中国工程院院士, 主要研究方向:药理学。Tel:0731-4805379 E-mai l:hhzhou2003 @163.com
基金资助:
国家自然科学基金项目(30801421); 教育部青年教师基金项目(20070533002)

Genetic polymorphisms of CYP2C8 and CYP2C9 in Chinese type 2 diabetes mellitus

HE Jun^1,2, ZHOU Wei¹, WANG Lian-ci¹, HE Ting-ye¹, WANG Dan¹, FAN Lan¹, ZHANG Wei¹, ZHOU Hong-hao¹

¹Institute of Clinical Pharmacology, Central South University, Changsha 410078, Hunan, China;
²Centre for Safety Evaluation and Research of Drugs, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100020,China;
³Shanghai Public Health Clinical Center, Shanghai 201508, China

Received:2009-02-05 Revised:2009-02-05 Published:2020-10-27

摘要/Abstract

摘要： 目的查明CYP2C9 、CYP2C8 等抗糖尿病药物主要代谢酶的基因多态性在中国2 型糖尿病(T2DM)人群中的分布频率和分布特征。方法运用多聚酶链反应-限制性长度多态性(PCR-RFLP)方法和变性高效液相色谱法(DHPLC)对222 名中国T2DM 患者进行了有功能意义的CYP2C8^＊3 、CYP2C8P404A 和CYP2C9^＊3, 以及可能存在功能意义的CYP2C8IVS2(-5insert t)突变体等等位基因型检测, 并计算了各等位基因的频率。结果 222名中国T2DM 患者的CYP2C8 基因中未检出CYP2C8^＊3 、P404A 型, CYP2C8IVS2(-5insert t)和CYP2C9^＊3 等位基因的频率分别为43.0 %、2.48 %, 二者突变等位基因在男、女性别分布中不存在差异(P >0.05), 同时为CYP2C8 IVS2(-5insertt)和CYP2C9^＊1^＊3 基因的频率为6.3 %, 该联合突变基因型的分布也不存在性别差异(P >0.05)。结论中国T2DM 患者中CYP2C9^＊3 的等位基因频率为2.48 %;未检出CYP2C8^＊3 和P404A 型,CYP2C8IVS2(-5insert t)突变体发生频率为43.0 %, 其是否影响CYP2C8 的代谢活力有待于进一步研究。

关键词: CYP2C8, 2 型糖尿病, 基因多态性, 多聚酶链反应-限制性长度多态性法, 变性高效液相色谱法

Abstract: AIM: To identify the frequencies and distributive characteristics of CYP2C8 and CYP2C9 in Chinese type 2 diabete mellitus. METHODS: The functional allele CYP2C8^＊3, CYP2C8P404A,CYP2C9^＊ 3 were detected by PCR-RFLP and DHPLC methods in 222 T2DM patients.The CYP2C8IVS 2 (-5insert t)whose function remains unclear was also detected.The frequency of all these alleles were calculated. RESULTS: The alleles of CYP2C8^＊3 and P404A were not found in 222 T2DM patients.The allelic frequency of CYP2C8IVS2 (-5insert t)and CYP2C9^＊3 were 43 % and 2.48 %, respectively.There was no significant difference between the male and female on CYP2C8 IVS2 (-5insert t)and CYP2C9^＊3 alleles. The allelic frequency of CYP2C8IVS2 (-5insert t) combined with CYP2C9^＊1^＊3 was 6.3 %.There was no significant difference between the male and female on it, too. CONCLUSION: The frequency of CYP2C9^＊3 was 2.48 % in Chinese T2DM patients. The alleles of CYP2C8^＊3 and P404 were not found. The incidence of CYP2C8IVS2 (-5insert t)mutant was 43.0 %, and whether it has influences on CYP2C8 metabolism activity needs further study.

Key words: CYP2C8, type 2 diabetes mellitus, genetic polymorphism, PCR-RFLP, DHPLC

中图分类号:

R587.1

何君, 周巍, 王练词, 何婷晔, 王丹, 范岚, 张伟, 周宏灏. 中国2 型糖尿病人中CYP2C8 、CYP2C9 基因多态性[J]. 中国临床药理学与治疗学, 2009, 14(3): 300-306.

HE Jun, ZHOU Wei, WANG Lian-ci, HE Ting-ye, WANG Dan, FAN Lan, ZHANG Wei, ZHOU Hong-hao. Genetic polymorphisms of CYP2C8 and CYP2C9 in Chinese type 2 diabetes mellitus[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(3): 300-306.

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