KCNJ11 E23K variant is associated with the therapeutic effect of sulphonylureas in Chinese type 2 diabetic patients

Abstract

The aim of the present study was to investigate the effect of the E23K variant of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene on gliclazide modified release (MR) treatment in newly diagnosed patients with type 2 diabetes mellitus (T2DM). A total of 108 diabetic patients with no history of antidiabetic medication was treated with gliclazide MR for 16 weeks and underwent follow up at Weeks 2, 4, 8, 12 and 16. All patients were genotyped for KCNJ11 E23K (rs5219). At baseline, patients with the KK genotype had higher blood glucose and lower serum insulin levels after oral glucose administration than patients with the EE and EK genotypes (P < 0.05 for all). During treatment, individuals with the KK genotype had lower fasting glucose levels and were more likely to attain the target fasting glucose level (Plog rank = 0.028) than E allele carriers. Patients with the KK genotype had larger augmentations in changes (Δ) in acute insulin response (P = 0.049) and Δ body mass index (P = 0.003). Moreover, patients with the EK genotype had a lower variance in changes in fasting insulin levels (P = 0.049) and homeostasis model assessment of β-cell function (P = 0.021) than those with the KK genotype. The findings of the present study suggest that the KCNJ11 E23K variant is associated with a greater effect of sulphonylurea treatment in newly diagnosed Chinese patients with T2DM.

Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes

“…Gliclazide MR initiates insulin secretion by closing potassium channels. Our previous research indicated that the KCNJ11 E23K variant is associated with the therapeutic effect of gliclazide in Chinese patients with T2DM [20] . However, the relationship between KCNQ1 and gliclazide has rarely been reported.…”

“…Moreover, it has been reported recently that KCNQ1 rs2237897 is related to the efficacy of gliclazide monotherapy in Chinese patient who are newly diagnosed with type 2 diabetes [19] . Our previous pharmacogenetic study of gliclazide demonstrated that KCNJ11 E23K can influence responses to gliclazide due to its effect on insulin secretion in Chinese patients who are newly diagnosed with T2DM [20] . The potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene is well known to encode a subunit of the inwardly rectifying potassium channel Kir6.2, which forms the K ATP channels in pancreatic β cells [20] .…”

“…Our previous pharmacogenetic study of gliclazide demonstrated that KCNJ11 E23K can influence responses to gliclazide due to its effect on insulin secretion in Chinese patients who are newly diagnosed with T2DM [20] . The potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene is well known to encode a subunit of the inwardly rectifying potassium channel Kir6.2, which forms the K ATP channels in pancreatic β cells [20] . However, KCNQ1 is the gene that encodes the pore-forming subunit of a voltage-gated K + channel (KvLQT1) that plays key roles in the repolarization of the cardiac action potential and water and salt transport in epithelial tissues.…”

“…All patients were diagnosed according to World Health Organization criteria [25] and recruited from the outpatient clinics in Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Detailed information in this study has been reported previously [20] . Diabetes education, including the introduction of T2DM and advice about diet and exercise, were provided to all patients.…”

“…The anthropometric measurements and clinical laboratory tests were described in detail previously [20] . In brief, anthropometric parameters containing height (m), weight (kg), waist and blood pressure were measured at baseline and at the final visit.…”