β3-AR Trp64Arg遗传多态性对T2DM患者罗格列酮疗效的影响  

The effect of β_3-AR Trp64Arg on rosiglitazone response in T2DM patients

作　　者：李慧华[1] 杨敏[1] 余敏[1] 周宏灏[1] 刘昭前[1] 

机构地区：[1]中南大学临床药理研究所,遗传药理学湖南省重点实验室,湖南长沙410078

出　　处：《中国药理学通报》2009年第3期317-321,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30572230);湖南省自然科学基金重点资助项目(No08JJ3058);湖南省“芙蓉学者计划”特聘教授基金资助项目(No湘教通[2006]312号)

摘　　要：目的探讨β3肾上腺素受体(β3-adrenergic receptor,β3-AR)Trp64Arg基因变异在中国健康人群和2型糖尿病(type2diabetes,T2DM)患者中的分布频率,查明该遗传多态性对罗格列酮在T2DM患者中疗效的影响。方法采用聚合酶链式反应-限制性片断长度多态性(polymerase chainreaction-restriction fragment length polymorphism,PCR-RFLP)对255名T2DM患者和148名健康对照者进行β3-ARTrp64Arg基因型分析,并在T2DM组中随机选取34名患者每天口服4mg罗格列酮,持续12wk。服药前和服药第12周末进行血糖、血胰岛素以及糖化血红蛋白等指标的测定。结果β3-AR Trp64Arg等位基因的发生频率符合Hardy-Wein-berg平衡,64Arg等位基因在T2DM组和健康对照组的频率分别为0.13和0.17。罗格列酮治疗12wk后,Trp64Arg基因型患者甘油三酯的下降值低于Trp64Trp型患者(P<0.05),但后者对低密度脂蛋白胆固醇(P<0.01)与脂联素(P<0.05)的作用优于Trp64Arg基因型患者。结论β3-AR Trp64Arg遗传多态性与中国汉族人群T2DM发病无明显相关性,但对2型糖尿病中罗格列酮的疗效存在一定影响。Aim To explore the impact of β3-adrenergic receptor （ADRB3） genetic variation on therapeutic efficacy of rosiglitazone in Chinese T2DM patients. Methods The genotypes of ADRB3 Trp64Arg in 255 T2DM patients and 148 healthy volunteers were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. Samples were randomly selected for direct DNA sequencing to identify the results of PCR-RFLP assay. 34 T2DM patients administrated orally 4 mg rosiglitazone daily for 12 consecutive weeks. The concentrations of fasting plasma glucose, postprandial plasma glucose, glycated hemoglobin, fasting serum insulin, postprandial serum insulin and so on in all T2DM subjects were determined before and after rosiglitazone treatment for 12 consecutive weeks. Results There were no significant differences in the distributive frequency of the ADRB3 Trp64Arg polymorphisms between T2DM patients and controls. Our results showed that ADRB3 Trp64Arg had bigger attenuated serum triglyceride （ P 〈 0. 05 ） and smaller attenuated low-density lipoprotein-cholesterol （P 〈 0. 01 ） as well as smaller enhanced adiponectin （P 〈 0. 05 ） compared with ADRB3 Trp64Atrp. Conclusion ADRB3 Trp64Arg genetic polymorphism are associated with therapeutic efficacy of multiple-dose rosiglitazone in Chinese T2DM patients.

关 键 词：Β3肾上腺素受体 基因多态性 2型糖尿病 罗格列 酮 

分 类 号：R392.11[医药卫生—免疫学]