Полиморфизм rs5219 гена KCNJ11 в прогнозировании риска развития сахарного диабета 2 типа

Abstract

The purpose — to study the possibility of using rs9939609 T/A polymorphisms of the FTO gene, rs5219 C/T of the KCNJ11 gene, rs1801282 C/G of the PPARG gene, rs8192678 G/A of the PPARGC1A gene, rs12255372 G/T and rs7903146 C/T of the TCF7L2 gene as markers for predicting the risk of developing type 2 diabetes mellitus in patients with T2DM risk factors. Material and methods. 112 overweight/obese patients from the Republic of Tatarstan (79% women and 21% men) aged 22 to 79 years participated in a single–center observational cohort 3-year prospective study. All patients were clinically examined, glucose tolerance test was performed, the level of glycated hemoglobin was determined, and polymorphisms rs9939609 T/A of the FTO gene, rs5219 C/T of the KCNJ11 gene, rs1801282 C/G of the PPARG gene, rs8192678 G/A of the PPARGC1A gene, rs12255372 G/T and rs7903146 C/T of the TCF7L2 gene were studied using PCR in real-time mode. Statistical analysis was performed with R 4.1.0 software. Univariable and multivariable logistic regression modeling were performed to evaluate association between outcomes and possible predictors. Area under the ROC-curve and Nagelkerke pseudo R-squared was used to compare prognostic performance of predictors. Results. According to the result of logistic regression (p=0.003), the carrier of the T allele KCNJ11 rs5219 is an independent risk factor for T2DM regardless of gender, age, waist circumference (WC), waist–hip ratio (WHR) and waist-to-height ratio (WHtR) and can be attributed as a marker of increased risk of T2DM. The inclusion of this polymorphism into T2DM clinical risk models, taking into account gender, age, maternal obesity, WHR and WHtR indices showed an increase of AUC from 0.74 to 0.78 (p=0.012) and from 0.73 to 0.79 (p=0.0056), respectively. Conclusion. The rs5219 polymorphism of the KCNJ11 gene can be used as an independent marker for predicting the risk of developing type 2 diabetes mellitus. The inclusion of this polymorphism in the risk model, which takes into account, in addition to the maternal obesity, the indices of WHtR or WHR, improves its predictive ability.