title: Variation in KCNQ1 is associated with therapeutic response to sulphonylureas.
abstract: BACKGROUND
  We aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment.
  
  
  METHODS
  Effect of 6-month sulphonylurea therapy in addition to metformin on glycemic control according to KCNQ1 genotypes was evaluated in 87 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. KCNQ1 rs163184 (T>G) polymorphism was determined by real-time PCR with melting analysis of unlabeled probe.
  
  
  RESULTS
  The reduction in fasting plasma glucose (ΔFPG) after 6-month sulphonylurea therapy significantly differed among 3 KCNQ1 genotype groups (ANOVA, p=0.017). In a recessive genetic model, carriers of the T-allele (TT+TG) achieved significantly lower FPG levels in comparison with patients with the GG genotype (6.95 ± 0.13 vs. 7.50 ± 0.21 mmol/L, p=0.033). Consequently, ΔFPG was significantly higher in the TT+TG group compared to the GG group (1.58 ± 0.13 vs. 1.04 ± 0.18 mmol/L, p=0.016). In multiple linear regression analysis KCNQ1 genotype (p=0.016) and baseline FPG (p<0.001) were the only significant independent predictors of ΔFPG (R2=0.48).
  
  
  CONCLUSIONS
  Our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to the variation in KCNQ1. The FPG response to sulphonylureas was significantly lower in carriers of the risk GG genotype.
authors.affiliation: Department of Internal Medicine 4, Faculty of Medicine, Safarik University, Kosice, Slovakia.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Schroner
authors.forename: Martina
authors.initials: M
authors.lastname: Dobrikova
authors.forename: Lucia
authors.initials: L
authors.lastname: Klimcakova
authors.forename: Martin
authors.initials: M
authors.lastname: Javorsky
authors.forename: Jozef
authors.initials: J
authors.lastname: Zidzik
authors.forename: Miriam
authors.initials: M
authors.lastname: Kozarova
authors.forename: Terezia
authors.initials: T
authors.lastname: Hudakova
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: D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D016014:Linear Models; D008687:Metformin / Q000627:therapeutic use; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D017931:DNA Primers; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D013453:Sulfonylurea Compounds; D008687:Metformin