Отсутствие ассоциации полиморфных локусов rs5219 гена KCNJ11 и rs757110 гена ABCC8 с долгосрочным ответом на терапию препаратами сульфонилмочевины в Новосибирской области

Abstract

Aim. Sulfonylureas (SU) are widely used in everyday clinical practice in treatment of patients with type 2 diabetes mellitus (T2DM). There is a considerable variability in SU effects, which may be caused by psychological, social, biological and genetic factors. The aim of the study was to investigate the association between rs5219 KCNJ11 gene and rs757110ABCC8 gene polymorphism and long-term response to SU-drugs of second and third generation in the Novosibirsk region. Materials and Methods. 326 patients with type 2 diabetes in the Novosibirsk region were examined. Patients were divided into 2 groups, depending on HbA1c level. The first group included patients with target HbA1c levels on SU monotherapy. The second group included patients who did not reach target HbA1c levels on the highest dose of SU. Genotyping of KCNJ11 (rs5219) and ABCC8 (rs757110) was performed by TaqMan real-time PCR (ICBFM SB RAS, Novosibirsk, Russia). Results. Patients with type 2 diabetes with a good response to SU-therapy compared to the group of patients with a poor response to SU-therapy were older (65.8±9.1 years vs. 61.6±7.9 years, p<0.01), had later onset of type 2 diabetes (59.7±9.2 years vs. 48.3±9.3 years, p <0.01), shorter duration of type 2 diabetes (6.1±4.8 years vs. 13.2±7.3 years, p<0.01) and weak insulin resistance: fasting insulin 9.7±6.9 mU/ml vs. 13.6±12.7 mU/ml (p<0.05), HOMA-IR 3.1±2.2 vs. 6.2±6.0 (p<0.01), triglycerides 1.76±0.83 mmol/l vs. 2.42±1.97 mmol/l (p <0.01). Statistically significant differences between KCNJ11 (rs5219) and ABCC8 (rs757110) genotypes and response to SU-therapy was not found. The frequency of risk allele T polymorphism rs5219 KCNG11 gene in patients with a good response to SU was 0.38 and in the patients with a poor response to SU -0.38 (χ2=0.02, р=0.89). The frequency of the risk allele G polymorphism rs757110 ABCC8 gene in patients with a good response to SU was 0.40 and in the patients with poor response to SU -0.37 (χ2=0.34, р=0.56). Conclusion. Patients with type 2 diabetes, who showed poor response to SU-therapy had a longer duration of diabetes, earlier diabetes onset, stronger insulin resistance compared to patients with a good response to SU-therapy. No correlation between rs5219 KCNJ11 gene and rs757110 ABCC8 gene polymorphism and long-term response to SU-therapy in T2DM patients in the Novosibirsk region was found.