脂联素基因启动子-11377(C/G)基因多态性与中国2型糖尿病和罗格列酮降糖疗效的相关性研究

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (1): 82-88.

脂联素基因启动子-11377(C/G)基因多态性与中国2型糖尿病和罗格列酮降糖疗效的相关性研究

孙红^1,2, 王少明¹, 庄捷¹, 刘海玲², 周宏灏², 刘昭前²

¹福建医科大学省立临床学院、福建省立医院, 福州350001, 福建;
²中南大学湘雅医学院临床药理研究所遗传药理学湖南省重点实验室, 长沙410078, 湖南

收稿日期:2009-09-07 修回日期:2009-11-18 出版日期:2010-01-26 发布日期:2020-09-21
通讯作者: 刘昭前, 男, 教授, 博导, 研究方向:遗传药理学。Tel:0731-84805380 E-mail: liuzhaoqian63@126.com
作者简介:孙红, 女, 硕士研究生, 药师, 研究方向: 临床药理学。Tel: 591-87557768-2037 E-mail: sunhong7777@126.com
基金资助:
国家自然科学基金资助项目(30572230)

Association of adiponectin allele -11377 (C/G)polymorphism with type 2 diabetes and rosiglitazone response in Chinese patients

SUN Hong^1,2, WANG Shao-ming¹, ZHUANG Jie¹, LIU Hai-ling², ZHOU Hong-hao², LIU Zhao-qian²

¹Department of Pharmacy, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, Fujian, China;
²Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University Xiang-Ya School of Medicine, Changsha 410078, Hunan, China

Received:2009-09-07 Revised:2009-11-18 Online:2010-01-26 Published:2020-09-21

摘要/Abstract

摘要： 目的探讨脂联素基因SN P-11377(C/G)与中国汉族2 型糖尿病(T2D)的关系及对罗格列酮降糖疗效的影响。方法应用PCR-RFLP 方法对255 名T2D 和120 名健康对照者进行-11377(C/G)基因分型, 选取42个不同基因型的T2D患者每天早饭时口服罗格列酮4 mg, 连续服药12 周。测定用药前后的TG 、空腹血糖(FPG)、餐后血糖(PPG)、糖化血红蛋白(HbAlc)、空腹胰岛素(FINS)、餐后胰岛素(PINS)、TC 、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDLC)、胰岛素抵抗指数(HOMA-IR)和脂联素水平。结果 T2D 组SNP-11377 等位基因频率与基因型频率明显高于健康对照组(P <0 .05), 并且随着G 等位基因的增加, 患者的脂联素水平(P <0 .01)明显降低, FINS(P <0 .05)和HOMA-IR水平(P <0 .05)明显增高。在服用罗格列酮后,CC 型FPG 、PPG 和HOMA-IR 的降低幅度明显高于突变型(CG +GG)(P <0 .05), 而CC 型脂联素升高幅度明显高于突变型(P <0 .01)。结论脂联素基因启动子-11377C/G 遗传变异与胰岛素抵抗和T2D 有关, 并且可能影响罗格列酮的降糖疗效。

关键词: 脂联素, 基因多态性, PCR-RFLP, 2型糖尿病, 罗格列酮

Abstract: AIM: To evaluate the impact of adiponectin allele C-11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D).METHODS: Patients with T2D (n =255) and 120 heal thy volunteers were enrolled to identify-11377C/Ggenotypes by polymerase chain reaction restricti on fragment length polymorphism assay.Forty-two T2D patients with different-11377C/G genotypes received orally rosig litazone as asingle-dose therapy (4 mg day-1 p.o.) for 12 weeks.The serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin(HbAlc), fasting serum insulin(FINS), postprandial serum insulin(PINS), total cholesterol(TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), homeostasis model assessment for insulin resistance (HOMA-IR), and adiponectin concent ration were determined before and after rosiglitazonet reatment. RESULTS: Compared with the health control group, the allele frequency of-11377(C/G) and the genotypic frequency were increased in T2D group(P <0.05), and as the Gallele gene increased, the adiponectin level was significantly decreased, and the level s of FINS and HOMA-IR were significantly increased in T2D patient s(P < 0.05).After treated with rosiglitazone, the degree of the decrease of the FPG (P <0.01),PPG (P <0.05)and HOMA-IR (P<0.05)levels in the CC genotype was significanthigher than that in the othergenotypes.However, the degree of the increase of the serum adiponect in concentration(P<0.01)in the CC genotype was sig nificantly higher than that in the other genotypes.CONCLUSION: These data suggest that the adiponectin allele-11377C/G polymorphisms sig nificantly associated with the pathogenesis of T2D, insulin resistance, and the the rapeuticefficacy of rosiglitazone in Chinese patients with T2D.

Key words: Adiponectin, Genetic polymorphism, PCR-RFLP, Type 2 diabetes, Rosiglitazone

中图分类号:

R587.1

孙红, 王少明, 庄捷, 刘海玲, 周宏灏, 刘昭前. 脂联素基因启动子-11377(C/G)基因多态性与中国2型糖尿病和罗格列酮降糖疗效的相关性研究[J]. 中国临床药理学与治疗学, 2010, 15(1): 82-88.

SUN Hong, WANG Shao-ming, ZHUANG Jie, LIU Hai-ling, ZHOU Hong-hao, LIU Zhao-qian. Association of adiponectin allele -11377 (C/G)polymorphism with type 2 diabetes and rosiglitazone response in Chinese patients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(1): 82-88.

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