Association of KCNJ11 E23K/rs5219 Gene Polymorphism with Type 2 Diabetes and Diabetes-Related Cardiovascular Disease

Monika Buraczynska, Sylwia Boczkowska, Wojciech Zaluska Department of Nephrology, Medical University of Lublin, Lublin, PolandCorrespondence: Monika Buraczynska, Department of Nephrology, Medical University of Lublin, Jaczewskiego 8, Lublin, 20-950, Poland, Tel/Fax +48 81 7244357, Email [email protected]: A potassium voltage-gated channel subfamily J member 11 (KCNJ11) is a candidate gene for diabetes and cardiovascular disease. We investigated the relationship of KCNJ11 E23K gene polymorphism with type 2 diabetes (T2DM) and diabetes-related cardiovascular disease (CVD).Methods: In this case–control study, the KCNJ11 E23K (rs5219) single nucleotide polymorphism was evaluated using the PCR-RFLP method in 780 patients with T2DM and 425 healthy controls. The genotype distribution was compared between subgroups of patients with CVD (524) and without CVD (256).Results: The genotyping results showed that the T allele and TT genotype were associated with the risk of T2DM (OR 1.26, p = 0.008 and OR 1.55, p = 0.0019, respectively). The T2DM group was analyzed according to the presence or absence of CVD. The T allele frequency was significantly higher in CVD+ than CVD− patients (49% vs 28%, p = 0.0001). The frequency of TT genotype in CVD+ subgroup was 20% compared to 8.5% in CVD−. This shows the significant correlation of the T allele with CVD in T2DM patients in all genetic association models. The OR for T allele was 2.44, p < 0.0001 representing 2.5-fold higher odds of CVD. For TT genotype, the OR 5.61, p < 0.0001 represents almost 6-fold higher risk of CVD development. The multiple logistic regression analysis showed that KCNJ11 E23K polymorphism was a significant risk predictor for CVD development (p < 0.0001).Conclusion: This is the first study of the relationship between KCNJ11 gene polymorphism and cardiovascular risk in T2DM patients in Polish population. The E23K (rs5219) polymorphism is associated with T2DM. It also increases the risk of cardiovascular disease in T2DM patients. If confirmed in other studies, it can be considered a potential marker for predicting the risk of CVD in T2DM patients.Keywords: KCNJ11 gene, type 2 diabetes, cardiovascular risk, single nucleotide polymorphism, genotyping