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

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.