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


CONCLUSIONS
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.
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
Qiong
Q
Huang
Ji-ye
JY
Yin
Xing-ping
XP
Dai
Qi
Q
Pei
Min
M
Dong
Zhi-guang
ZG
Zhou
Xi
X
Huang
Min
M
Yu
Hong-hao
HH
Zhou
Zhao-qian
ZQ
Liu
D000328:Adult; D000368:Aged; D044466:Asian People; D002219:Carbamates / Q000627:therapeutic use*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics*; D012307:Risk Factors
D002219:Carbamates; D007004:Hypoglycemic Agents; C498779:IGF2BP2 protein, human; D007328:Insulin; D010880:Piperidines; D016601:RNA-Binding Proteins; C072379:repaglinide