title: KCNJ11 gene E23K variant and therapeutic response to sulfonylureas.
abstract: OBJECTIVE
  Potassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive potassium (K(ATP)) channel encoded by KCNJ11 gene is a therapeutical target for sulfonylureas. KCNJ11 E23K polymorphism was associated with type 2 diabetes in genetic association studies. The aim of the present pharmacogenetic study was to examine the effect of sulfonylurea treatment on glycemic control in relationship to KCNJ11 E23K variant.
  
  
  METHODS
  One hundred and one patients with type 2 diabetes who failed to achieve HbA1c<7% on previous metformin monotherapy were included to the study. Sulfonylurea drug was given in addition to metformin. The main outcome of the study was reduction in HbA1c level (ΔHbA1c) after 6-month sulfonylurea therapy. KCNJ11 genotypes were determined by real-time PCR with melting curve analysis.
  
  
  RESULTS
  After 6-month treatment, KCNJ11 K-allele carriers had higher decrease in HbA1c compared with EE homozygotes in the dominant genetic model (1.04±0.10 vs. 0.79±0.12%, p=0.036). In the log-additive model, greater mean reduction in HbA1c by 0.16% (95% CI 0.01-0.32, p=0.038) per each K-allele was observed. The relationship of treatment response with KCNJ11 genotype was also significant in the biggest subgroup of patients treated with gliclazide (n=55).
  
  
  CONCLUSIONS
  Carriers of the KCNJ11 K-allele have better therapeutic response to gliclazide. This observation might help to identify patients who will have the highest benefit from sulfonylurea treatment.
authors.affiliation: Department of Internal Medicine 4, Faculty of Medicine, Safarik University, Kosice, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Javorsky
authors.forename: Lucia
authors.initials: L
authors.lastname: Klimcakova
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Schroner
authors.forename: Jozef
authors.initials: J
authors.lastname: Zidzik
authors.forename: Eva
authors.initials: E
authors.lastname: Babjakova
authors.forename: Maria
authors.initials: M
authors.lastname: Fabianova
authors.forename: Miriam
authors.initials: M
authors.lastname: Kozarova
authors.forename: Ruzena
authors.initials: R
authors.lastname: Tkacova
authors.forename: Jan
authors.initials: J
authors.lastname: Salagovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Tkac
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005907:Gliclazide / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D000099161:Kcnj11 Channel
chemical_list: D005907:Gliclazide; D007004:Hypoglycemic Agents; D008687:Metformin; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel