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


CONCLUSIONS
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.
He
Ya-yi
YY
Department of Endocrinology and Metabolism, the Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China.
Zhang
Rong
R
Shao
Xin-yu
XY
Hu
Cheng
C
Wang
Cong-rong
CR
Lu
Jun-xi
JX
Bao
Yu-qian
YQ
Jia
Wei-ping
WP
Xiang
Kun-san
KS
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002219:Carbamates / Q000627:therapeutic use*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D002219:Carbamates; D004247:DNA; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010880:Piperidines; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C072379:repaglinide