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

被引：54

作者：

He, Ya-yi ^{[1
]}

Zhang, Rong ^{[1
]}

Shao, Xin-yu ^{[1
]}

Hu, Cheng ^{[1
]}

Wang, Cong-rong ^{[1
]}

Lu, Jun-xi ^{[1
]}

Bao, Yu-qian ^{[1
]}

Jia, Wei-ping ^{[1
]}

Xiang, Kunsan ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai 200233, Peoples R China

来源：

ACTA PHARMACOLOGICA SINICA | 2008年 / 29卷 / 08期

关键词：

repaglinide; polymorphism; pharmacogenomics; type; 2; diabetes;

D O I：

10.1111/j.1745-7254.2008.00840.x

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：983 / 989

页数：7

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