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.