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Controlled Clinical Trial
. 2012 Sep;74(3):501-9.
doi: 10.1111/j.1365-2125.2012.04202.x.

NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes

Zhi-Cheng Gong  1 , Qiong Huang, Xing-Ping Dai, Guang-Hua Lei, Hong-Bin Lu, Ji-Ye Yin, Xiao-Jing Xu, Jian Qu, Qi Pei, Min Dong, Bo-Ting Zhou, Jie Shen, Gan Zhou, Hong-Hao Zhou, Zhao-Qian Liu
Affiliations
Controlled Clinical Trial

NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes

Zhi-Cheng Gong et al. Br J Clin Pharmacol. 2012 Sep.

Abstract

Aims: We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients.

Methods: Three 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.

Results: The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 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 of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1) , P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1), P < 0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1), P < 0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1), P < 0.05) (-8.20, -4.89 vs.-3.92, -1.20).

Conclusions: The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.

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Figures

Figure 1
Figure 1
Comparison of levels, before repaglinide treatment, of fasting serum insulin (a) and postprandial serum insulin (b) in type 2 diabetes mellitus (T2DM) patients with different NeuroD1/BETA2 A45T genotypes and postprandial serum insulin (c) in T2DM patients with different PAX4 R121W genotypes
Figure 2
Figure 2
Comparison of differential values (postadministration minus pre-administration) of fasting plasma glucose (a) and postprandial plasma glucose (b) between A/A genotype and A/T+T/T genotypes of NeuroD1/BETA2 A45T polymorphism and postprandial plasma glucose (c) between R/R genotype and R/W+W/W genotypes of PAX4 R121W polymorphism in T2DM patients after repaglinide treatment
See this image and copyright information in PMC

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