KCNJ11 gene E23K variant and therapeutic response to sulfonylureas

Abstract Aims 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. Patients and methods One hundred and one patients with type 2 diabetes who failed to achieve HbA1c  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.