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

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.

• Authors: Zhi-Cheng Gong, 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
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 74 Issue 3 Pg. 501-9 (Sep 2012) ISSN: 1365-2125 [Electronic] England
• PMID: 22296034 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Blood Glucose
• Carbamates
• Homeodomain Proteins
• Hypoglycemic Agents
• NEUROD1 protein, human
• PAX4 protein, human
• Paired Box Transcription Factors
• Piperidines
• repaglinide

Topics

• Adult
• Aged
• Alleles
• Asian People
• Basic Helix-Loop-Helix Transcription Factors (genetics)
• Blood Glucose (drug effects)
• Carbamates (pharmacology)
• Case-Control Studies
• China
• Diabetes Mellitus, Type 2 (drug therapy, genetics)
• Female
• Genotype
• Homeodomain Proteins (genetics)
• Humans
• Hypoglycemic Agents (pharmacology)
• Male
• Middle Aged
• Paired Box Transcription Factors (genetics)
• Piperidines (pharmacology)
• Polymorphism, Genetic
• Polymorphism, Restriction Fragment Length