Variation in KCNQ1 is associated with therapeutic response to sulphonylureas

• Published in: Medical science monitor 2011-07, Vol.17 (7), p.CR392-CR396
• Main Authors: Schroner, Zbynek, Dobrikova, Martina, Klimcakova, Lucia, Javorsky, Martin, Zidzik, Jozef, Kozarova, Miriam, Hudakova, Terezia, Tkacova, Ruzena, Salagovic, Jan, Tkac, Ivan
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Blood Glucose - analysis; Clinical Research; Diabetes Mellitus, Type 2 - drug therapy; DNA Primers - genetics; Genotype; Humans; KCNQ1 Potassium Channel - genetics; KCNQ1 Potassium Channel - metabolism; Linear Models; Metformin - therapeutic use; Pharmacogenetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Sulfonylurea Compounds - therapeutic use
• ISSN: 1234-1010; 1643-3750
• DOI: 10.12659/MSM.881850

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. 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. 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