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IGF2BP2 变异影响瑞格列奈在中国人群中的反应和 2 型糖尿病风险。

IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population.

机构信息

Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.

出版信息

Acta Pharmacol Sin. 2010 Jun;31(6):709-17. doi: 10.1038/aps.2010.47.

Abstract

AIM

To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus (T2DM) and the repaglinide therapeutic efficacy in Chinese T2DM patients.

METHODS

A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment.

RESULTS

The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls (P<0.05 and P<0.001, respectively). The effects of the repaglinide treatment on FPG (P<0.05) and PPG (P<0.05) were reduced in patients with the rs1470579 AC+CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT+TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS (P<0.01) compared with GG genotype subjects.

CONCLUSION

The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients.

摘要

目的

探讨胰岛素样生长因子 2mRNA 结合蛋白 2(IGF2BP2)rs1470579 和 rs4402960 多态性与 2 型糖尿病(T2DM)的发生以及格列美脲治疗中国 T2DM 患者的疗效是否相关。

方法

采用病例对照研究,共纳入 350 例 T2DM 患者和 207 例健康志愿者,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测 IGF2BP2 rs1470579 和 rs4402960 多态性。随机选择 42 例患者进行为期 8 周的格列美脲治疗(3mg/d)。治疗前后测定空腹血糖(FPG)、餐后血糖(PPG)、糖化血红蛋白(HbAlc)、空腹血清胰岛素(FINS)、餐后血清胰岛素(PINS)、胰岛素抵抗指数(HOMA-IR)、血清甘油三酯、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-c)和高密度脂蛋白胆固醇(HDL-c)。

结果

T2DM 患者 IGF2BP2 rs1470579 C 等位基因和 rs4402960 T 等位基因的频率高于健康对照组(P<0.05 和 P<0.001)。与 AA 基因型携带者相比,rs1470579 AC+CC 基因型患者格列美脲治疗对 FPG(P<0.05)和 PPG(P<0.05)的影响降低。与 GG 基因型患者相比,rs4402960 GT+TT 基因型患者格列美脲治疗对 PINS 的影响增强(P<0.01)。

结论

IGF2BP2 rs1470579 和 rs4402960 多态性可能与 T2DM 的发生有关,这些多态性可能影响中国 T2DM 患者格列美脲的治疗效果。

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