Inflammatory Biomarkers in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Faction

Abstract

Aim. To verify the relationship between gene polymorphisms of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) with inflammation markers and codependent metabolic variables in patients with type 2 diabetes mellitus and chronic heart failure (CHF).Material and methods. This study included 154 patients (mean age, 69.1±3.2 years). The control group consisted of 47 patients with metabolic syndrome (MS) without CHF; the 2nd group included 56 patients with CHF with preserved ejection fraction (CHFpEF); and the 3rd group consisted of 51 patients with CHF with reduced ejection fraction (CHFrEF). The rs1800629 polymorphism of the TNF-α gene (TNF-α: G308A) was studied in real time by the polymerase chain reaction (PCR) method and the rs1800795 polymorphism of the IL-6 gene (IL-6: 174 G>C) was studied by PCR with the electrophoretic detection. The frequencies of polymorphic alleles were compared with the clinical blood test results, plasma concentrations of C-reactive protein (CRP), TNF-α, leptin, and fibrinogen. Differences between the groups were determined using the F test. Relationships between individual studied parameters were identified using the regression analysis.Results. In most patients, the occurrence of gene polymorphisms was eident as increased plasma concentrations of biomarkers. An association was found between the TNF-α gene polymorphism (G308A) and an increase in plasma TNF-α and between the IL-6 gene polymorphism (174 C>G) and an increase in plasma CRP. In the CHFpEF group, the rs1800629 gene polymorphism was observed in 55% of patients, among whom 93% had increased TNF-α. The rs1800795 gene polymorphism was observed in 82% of CHFpEF patients, among whom 21% had increased CRP. In the CHFrEF group, the G308A transition in the TNF-α gene was observed in 53% of patients; an increase in the respective cytokine was noted in 67% of patients; the IL-6 gene polymorphism 174 C>G was found in 78%, however, only 14% of patients with this polymorphism had also increased CRP. In the control group, the TNF-α G308A gene polymorphism was found in 30% of patients, while an increase in free TNF-α was associated with this polymorphism in 50% of patients; the IL-6 174 C>G gene polymorphism was detected in 78%, while no increase in the CRP level was observed in this group. This demonstrates a high probability of the TNF-α G308A gene polymorphism occurrence in patients with CHF.Conclusion. Inflammatory markers are important predictors of CHF. The most significant predictor was the TNF-α G308A gene polymorphism, which was observed in more than 50% of patients, the majority of whom had an increase in plasma TNF-α