title: Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, the Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China.
authors.forename: Ya-yi
authors.initials: YY
authors.lastname: He
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Xin-yu
authors.initials: XY
authors.lastname: Shao
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.forename: Cong-rong
authors.initials: CR
authors.lastname: Wang
authors.forename: Jun-xi
authors.initials: JX
authors.lastname: Lu
authors.forename: Yu-qian
authors.initials: YQ
authors.lastname: Bao
authors.forename: Wei-ping
authors.initials: WP
authors.lastname: Jia
authors.forename: Kun-san
authors.initials: KS
authors.lastname: Xiang
mesh_terms: 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
chemical_list: 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