Vascular endothelial growth factor (VEGF-2578А/С) gene polymorphism in combination with cytokine gene polymorphisms among patients with rheumatoid arthritis

Abstract

Objective: to study the distribution of the genotypes of the vascular endothelial growth factor (VEGF) gene and their combinations with those of other cytokines among patients with rheumatoid arthritis (RA) and healthy individuals. Subjects and methods. 509 Europeoid women from the eastern regions of Russia, including 374 healthy individuals aged 23-64 years and 135 RA patients aged 27-66 years, were examined. The single nucleotide polymorphism in the promoter region of the genes of VEGC -2578 C/A, tumor necrosis factor-а (TNF-а) -863 C/A, TNF-а -308 G/A, TNF-а -238 G/A, and interleukin (IL) 1β -31 С/T, IL4 -590 С/T, IL6-174 G/C, IL10-1082 G/A, and IL10-592А/С was studied by restriction fragment length polymorphism analysis. Results. Analysis of the frequency of the genotypes of VEGF in combination with other genotypes has revealed a number of highly significant genetic differences between the groups of healthy individuals and RA patients. Among the combined genetic signs (CGS), whose frequency is significantly increased in RA, there is a predominance of heterozygous CA genotypes at the polymorphic position of VEGF -2578 C/A. Among the CGS positively associated with RA, which include homozygous VEGF -2578 variants, there is a preponderance of AA genotypes whereas all 100% of the homozygous genotypes, whose frequency is significantly decreased in RA, correspond to the variant of СС. The CGS whose frequency is altered in RA along with VEGF genotypes most commonly include the genotypes of IL1s, IL4, IL10, IL6, and TNF-а. Conclusion. The pathogenesis of RA calls for comprehensive investigation of the role of the angiogenesis and inflammation regulation genes.