中国2型糖尿病人中CYP2C8、CYP2C9基因多态性  

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

作　　者：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] 

机构地区：[1]中南大学临床药理研究所 [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

出　　处：《中国临床药理学与治疗学》2009年第3期300-306,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(30801421);教育部青年教师基金项目(20070533002)

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(-5i-nsert t)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。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 fiequency 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 （-Sinsert 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.

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 

分 类 号：R587.1[医药卫生—内分泌]