Combinations of polymorphisms in vascular endothelial growth factor gene and genes of its receptors (VEGF/VEGFR) at development of cardiovascular risk in rheumatoid arthritis patients

Abstract

Introduction. Cardiovascular risk (CR) development in rheumatoid arthritis patients (RA) is considerably increased. Major factors of CR cannot explain the given phenomenon completely, therefore features of system inflammatory processes which it is characteristic for RA are analyzed. The considered of synovium angiogenesis and of angiogenic signaling pathways, including mediated by vascular endothelial growth factor VEGF and its receptors system VEGFR is one of the important factors of RA immunopathogenesis.

Aim. Analysis of single-nucleotide polymorphisms of VEGF (rs699947, rs3025039), its receptors KDR (rs10020464, rs11133360), NRP-2 (rs849530, rs849563, rs16837641) genes and associations of their combinations with CR development at RA patients.

Material and methods. 135 RA patients (median age is 55 years, duration of disease is 7 years) are surveyed. The increase of CR is revealed at 45.2 % of patients. Genotyping was carried out with restriction analysis of fragment length polymorphism (RFLP) and Real-time PCR (RT-PCR) with TaqMan.

Results. The complex genotypes which frequency are increased in group of high cardiovascular risk patients concerning RA patients with low cardiovascular risk were revealed. The highest relations of chances of high CR development at carriers of complex KDR 14011TT:NRP2 13581TT:VEGF-2578CC, and early relations high CR at patients with KDR 17693CC:KDR 14011TC:NRP2 13581TT:VEGF-2578CA: VEGF+936CC. Protective genotypes, patients with which are steady against high CR development even at long current RA, are revealed also.

Conclusion. Polymorphic positions of angiogenesis mediators genes can in common influence change of certain CR at patients with RA.

Keywords:rheumatoid arthritis; cardiovascular risk; VEGF gene polymorphism; VEGFR genes; KDR polymorphism; NRP2 polymorphism

For citation: Shevchenko A.V., Konenkov V.I., Prokof’ev V.F., Korolev M.A., Omelchenko V.O. Combinations of polymorphism in vascular endothelial growth factor gene and genes of it receptors (VEGF/VEGFR) at development of cardiovascular risk in rheumatoid arthritis patients. Immunologiya. 2019; 41 (3): 206-14. DOI: 10.33029/0206-4952-2020-41-3-206-214 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

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