Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients.

Abstract

AIM:

The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16-3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes.

METHODS:

A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment.

RESULTS:

Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P=0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P=0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16-3 C/C versus the T/C and T/T genotypes (P=0.0372 and 0.0274, respectively).

CONCLUSION:

The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16-3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.

• Authors: Ya-yi He, Rong Zhang, Xin-yu Shao, Cheng Hu, Cong-rong Wang, Jun-xi Lu, Yu-qian Bao, Wei-ping Jia, Kun-san Xiang
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 29 Issue 8 Pg. 983-9 (Aug 2008) ISSN: 1745-7254 [Electronic] United States
• PMID: 18664331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-Binding Cassette Transporters
• Carbamates
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Kir6.2 channel
• Piperidines
• Potassium Channels, Inwardly Rectifying
• Receptors, Drug
• Sulfonylurea Receptors
• repaglinide
• DNA

Topics

• ATP-Binding Cassette Transporters (genetics)
• Carbamates (therapeutic use)
• DNA (biosynthesis, genetics)
• Diabetes Mellitus, Type 2 (drug therapy, genetics)
• Female
• Gene Frequency
• Genotype
• Glycated Hemoglobin (metabolism)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Male
• Middle Aged
• Piperidines (therapeutic use)
• Polymorphism, Genetic (genetics)
• Potassium Channels, Inwardly Rectifying (genetics)
• Receptors, Drug (genetics)
• Sulfonylurea Receptors