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

  
@article{APS4702,
	author = {Ya-yi He and Rong Zhang and Xin-yu Shao and Cheng Hu and Cong-rong Wang and Jun-xi Lu and Yu-qian Bao and Wei-ping Jia and Kun-san Xiang},
	title = {Association of  KCNJ11  and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients},
	journal = {Acta Pharmacologica Sinica},
	volume = {29},
	number = {8},
	year = {2016},
	keywords = {},
	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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/4702}
}