KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic efficacy of repaglinide in Chinese patients with type 2 diabetes.

Abstract

This study showed that the polymorphisms KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) are associated with a heightened risk of developing type 2 diabetes mellitus (T2DM). We also explored the effects of these polymorphisms on the efficacy of repaglinide therapy in Chinese patients with T2DM. A total of 259 patients with T2DM and 188 healthy controls were genotyped. Forty patients with various genotypes were randomly selected to undergo an 8-week repaglinide treatment regimen. Patients with the G allele of the KCNJ11 Lys23Glu polymorphism showed higher levels of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) (P < 0.05). After repaglinide treatment, patients with the GA or AA genotype showed higher levels of FPG, PPG, and glycated hemoglobin (HbA(1c)) compared with patients with the GG genotype (P < 0.05). Patients with the C allele of TCF7L2 rs290487(C/T) had higher total cholesterol levels and lower body mass index (BMI) (P < 0.05). In patients with the TT genotype, the drug showed better efficacy with respect to levels of fasting insulin, triglycerides, and low-density lipoprotein cholesterol (LDL-c) than in patients with the CC or CT genotype (P < 0.05). The KCNJ11 and TCF7L2 polymorphisms were associated with repaglinide efficacy.

• Authors: M Yu, X-J Xu, J-Y Yin, J Wu, X Chen, Z-C Gong, H-Y Ren, Q Huang, F-F Sheng, H-H Zhou, Z-Q Liu
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 87 Issue 3 Pg. 330-5 (Mar 2010) ISSN: 1532-6535 [Electronic] United States
• PMID: 20054294 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Carbamates
• Kir6.2 channel
• Piperidines
• Potassium Channels, Inwardly Rectifying
• TCF Transcription Factors
• TCF7L2 protein, human
• Transcription Factor 7-Like 2 Protein
• Glutamic Acid
• repaglinide
• Lysine

Topics

• Adult
• Alleles
• Amino Acid Substitution (genetics)
• Asian People (genetics)
• Blood Glucose (drug effects, genetics)
• Carbamates (therapeutic use)
• Diabetes Mellitus, Type 2 (blood, drug therapy, genetics)
• Female
• Glutamic Acid (genetics)
• Humans
• Lysine (genetics)
• Male
• Middle Aged
• Piperidines (therapeutic use)
• Polymorphism, Genetic (genetics)
• Potassium Channels, Inwardly Rectifying (genetics)
• Risk Factors
• TCF Transcription Factors (genetics)
• Transcription Factor 7-Like 2 Protein
• Treatment Outcome