Gene polymorphism and serum levels of some angiogenic growth factors and pro- and anti-inflammatory cytokines in patients with post-infarction cardiac remodeling

Abstract

Aim. To investigate the polymorphic variants of IL10, FGF2, VEGFD, TRAIL, SELE, TNFA and TNFβ genes in patients with primary ST-segment elevation myocardial infarction (MI) (STEMI) and to evaluate their association with late post-infarction cardiac remodeling.Material and methods. The study includes 74 patients age 61±10,7 years with primary STEMI. Percutaneous coronary intervention with restoration of infarct-related artery patency was performed in all patients after 60 (40; 80) minutes since admission to the hospital. Serum levels of fibroblast growth factor (FGF), interleukin-10 (IL-10), tumor necrosis factor family cytokines (TNF-α, TNF-β and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)) were measured with the Multiplex Instrument FLEXMAP 3D system (Luminex Corporation) and the MILLIPLEX Human Cytokine/Chemokine Panel II on the 1st, 7th day of early post-MI period and after 6 and 12 months. The late adverse cardiac remodeling was determined after 12 months of long-term post-MI period according to 2D echo­cardiography. The increase in left ventricular end-diastolic volume by 15% or more by 12 months was considered late adverse cardiac remodeling. The patients were genotyped by 16 single-nucleotide polymorphisms (SNPs) in the TNFβ, TNF, Il10, TNFRSF1B, VEGFD, TRAIL, FGF2, SELE genes.Results. Adverse cardiac remodeling occurred in 19 patients (25,7%). The genetic association analysis revealed the significant association of rs1800629 TNFA (χ2=4,748; p=0,029), rs5353 SELE (χ2=10,85; p=0,004) and rs6632528 VEGFD (χ2=8,127; p=0,017) with an increased risk of STEMI. Higher concentration of IL-10 was detected on the 7th day of MI (p=0,05) and 6 months later (p=0,028) in A/T rs3024492 genotype carriers, as well as FGF in T/T rs13122694 genotype carriers by the 6th month after the event (p=0,04). The dependence of the main LV indicators on the distribution of polymorphism genotypes rs3024492 IL10, rs13122694 FGF2 and rs4830939 VGEFD was discovered. In the first 24 hours of MI in rs3024492 IL10 heterozygotes, LV contractile function was worse in comparison with T/T genotype carriers. Also, carriers of the T/T rs13122694 FGF2 genotype were distinguished by higher LV ejection fraction, longitudinal global LV deformation and lower of LV end-systolic index in the early post-infarction period. In the long-term post-infarction period, T/T rs4830939 VEGFD carriers differed in a greater LV dilation than carriers of the C/C and C/T genotypes.Conclusion. The study showed the contribution of polymorphism of the inflammation system genes to a predisposition to STEMI — both at the levels of phenotype and individual signs.