NeuroD1A45T andPAX4R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes
Authors: Gong Zhi‐Cheng , Huang Qiong , Dai Xing‐Ping , Lei Guang‐Hua , Lu Hong‐Bin , Yin Ji‐Ye , Xu Xiao‐Jing , Qu Jian , Pei Qi , Dong Min , Zhou Bo‐Ting , Shen Jie , Zhou Gan , Zhou Hong‐Hao , Liu Zhao‐Qian 
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Repaglinide is an insulin secretagogue agent widely used in the treatment of type 2 diabetes mellitus (T2DM). Obvious interindividual differences in the therapeutic efficacy of and adverse reactions to repaglinide were observed in Chinese T2DM patients.

• There are no reports showing the influence of genetic variations ofNeuroD1/BETA2A45T andPAX4R121W on repaglinide response in Chinese T2DM patients.

WHAT THIS STUDY ADDS

• This study aimed to investigate the association of genetic polymorphisms ofNeuroD1/BETA2A45T andPAX4R121W with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients.

• TheNeuroD1/BETA2A45T andPAX4R121W polymorphisms were correlated with repaglinide therapeutic efficacy in Chinese T2DM patients.

AIMSWe aimed to determine whetherNeuroD1/BETA2andPAX4polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients.

METHODSThree hundred and sixty‐eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty‐three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day−1). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low‐density lipoprotein‐cholesterol and high‐density lipoprotein‐cholesterol were determined before and after repaglinide treatment.

RESULTSThe allelic frequency ofNeuroD1/BETA2T45 was higher in T2DM patients than in the control subjects [13.45vs.6.82%,P< 0.01, odds ratios = 2.342 (1.365, 4.019),P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele ofNeuroD1/BETA2A45T polymorphism showed higher FINS (13.46 ± 12.57vs.10.04 ± 7.09 mU l−1,P< 0.05) (11.67, 14.83vs.8.38, 11.37) and PINS (52.11 ± 40.93vs.68.66 ± 43.87 mU l−1,P< 0.05) (44.89, 58.35vs.55.35, 88.87) than individuals with the T allele. ThePAX4R121W R allele carriers had higher PINS (52.11 ± 40.93vs.68.66 ± 43.87 mU l−1,P< 0.05) (44.89, 58.35vs.55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele ofNeuroD1/BETA2A45T polymorphisms had attenuated efficacy on fasting plasma glucose (−2.79 ± 2.14vs.−0.99 ± 1.80 mmol l−1,P< 0.01) (−3.53, −1.84vs.−1.99, −0.13) and postprandial plasma glucose (−6.71 ± 5.90vs.−2.54 ± 3.39 mmol l−1,P< 0.01) (−9.28, −4.62vs.−4.34, −0.84). Patients with the RR genotype ofPAX4R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (−6.53 ± 6.52vs.−2.95 ± 1.17 mmol l−1,P< 0.05) (−8.20, −4.89vs.−3.92, −1.20).

CONCLUSIONSTheNeuroD1/BETA2andPAX4polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.