视黄醇结合蛋白4基因多态性对中国2型糖尿病患者服用罗格列酮疗效的影响(英文)  

Impact of retinol binding protein 4 polymorphism on rosiglitazone response in Chinese Type 2 diabetic patients

作　　者：周芳[1,2] 黄琼[1] 戴幸平[1] 尹继业[1] 吴静[3] 周宏灏[1] 龚志成[4] 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,长沙410078 [2]岳阳职业技术学院生物医药系,湖南岳阳414000 [3]湘雅医院内分泌科,长沙410008 [4]湘雅医院药剂科,长沙410008

出　　处：《中南大学学报（医学版）》2011年第10期949-957,共9页Journal of Central South University ：Medical Science

基　　金：supported by the National High-Tech R&D Program of China(“863”Program)(2009AA22704);the National Natural Science Foundation of China(30873089,81173129);the Program for Changjiang Scholars and Innovative Research Team in University(IRT0946);the Open Foundation of Innovative Platform in University of Hunan Province of China(10K078);the Science and Technology Plan Key Grant of Hunan Province of China(2009TP4068-2);the Fundamental Research Funds for the Central Universities(201023100001)

摘　　要：目的:研究视黄醇结合蛋白4(retinol binding protein 4,RPB4)基因rs3758539G-803A和rs10882283T-179G多态性对中国人群2型糖尿病患者使用罗格列酮疗效的影响。方法:使用PCR-RFLP方法对472名2型糖尿病患者和198名健康对照者进行RPB4基因G-803A和T-179G多态性位点的基因分型。随机选择42名携带不同RBP4基因型的2型糖尿病患者给予12周每天4 mg的罗格列酮口服治疗。检测用药前后空腹血糖(fasting plasma glucose,FPG)、餐后血糖(postprandial plasma glucose,PPG)、空腹胰岛素(fastingserum insulin,FINS)、餐后胰岛素(postprandial serum insulin,PINS)、糖化血红蛋白(glycated hemoglobin,HbAlc)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein-cholesterol,LDL-c))和高度脂蛋白胆固醇(high-density lipoprotein-cholesterol,HDL-c)等指标。结果:携带RBP4 G-803A GG基因型的患者其TG和LCL-c水平显著低于GA+AA基因型患者。携带T-179G TT基因型的患者其腰臀比、FPG和FINS值显著低于TG+GG基因型患者。携带RBP4 G-803A GG基因型的患者服用罗格列酮后FPG和FINS下降值优于GA+AA基因型患者。携带T-179G TG+GG基因型的患者服用罗格列酮后的HbAlc下降值优于TT基因型患者。结论:RBP4 G-803A和T-179G基因多态性与2型糖尿病相关且影响罗格列酮的疗效。Objective To explore the association between rs3758539G-803A and rs10882283T-179G polymorphism of retinol binding protein 4（RBP4） and rosiglitazone response in Chinese type 2 diabetes mellitus（T2DM） patients.Methods A total of 472 Chinese T2DM patients and 198 healthy subjects were enrolled to identify G-803A and T-179G genotypes using a polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） assay.Forty-two T2DM patients with different G-803A or T-179G genotypes were selected to undergo a 12-week rosiglitazone treatment（4 mg/d）.Serum fasting plasma glucose（FPG）,postprandial plasma glucose（PPG）,fasting serum insulin（FINS）,glycated hemoglobin（HbAlc）,postprandial serum insulin（PINS）,triglyceride（TG）,low-density lipoprotein-cholesterol（LDL-c）,and high-density lipoprotein-cholesterol（HDL-c） were determined before and after the rosiglitazone treatment.Results T2DM patients with RBP4 G-803A GG genotype showed lower TG and LDL-c concentrations compared with that in the GA＋AA genotype subjects.T2DM patients with RBP4 T-179G TT genotype showed lower waist-to-hip ratio（WHR）,FPG and FINS values compared with that in the TG＋GG genotype individuals.Patients with GG genotype of RBP4 G-803A had an enhanced rosiglitazone efficacy on FPG and FINS compared with that in the GA＋AA genotype group.Patients with RBP4 T-179G TG＋GG genotype showed an enhanced rosiglitazone efficacy on HbAlc level compared with that in the TT genotype group.Conclusion RBP4 G-803A and T-179G polymorphism might be associated with the development of T2DM and affect the therapeutic efficacy of rosignitazone in Chinese T2DM patients.

关 键 词：视黄醇结合蛋白4 基因多态性 2型糖尿病 罗格列酮 疗效 

分 类 号：R587.1[医药卫生—内分泌]