Genetic factors of angiogenic dysregulation in women with rheumatoid arthritis

Aim. To study genotype distribution in the MMP and VEGF genes, angiogenesis regulators, and their combinations with genotypes in other cytokines genes with proangiogenic activity in female patients with rheumatoid arthritis (RA) and healthy individuals. Subjects and methods. 509 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 135 female patients aged 27-66 years with RA, were examined. TNF-alpha gene promoter single nucleotide polymorphisms (SNP) -863 C -> A, TNFA -308 G -> A, TNFA -238 G -> A; IL1 beta -31 C -> T, IL4 -590 C -> T, IL6 -174 G -> C, IL10 -1082 G -> A and IL10 -592 A -> C; VEGF -2578 C -> A, VEGF +936 C -> T; MMP 2 -1306 C -> T, MMP 9 -1562 C -> T were investigated by the restriction analysis of amplification products. Results. The patients with RA show a preponderance of the combinations of genotypes in vascular endothelial growth factor (VEGF) synthesis inducers, which are related to the high-level production of this factor, and those of genotypes in the degradation of the extracellular matrix of MMP2 and MMP9, which characterize the low baseline elaboration of matrix metalloproteinases (MMP) with a high capability for their induced synthesis, which is specific to the dysregulated states of the angiogenesis control system. Along with MMP and VEGF genotypes, the combinations most commonly contain IL1 beta, IL4, IL10, IL6, and TNF-alpha genotypes. Conclusion. The study of the pathogenesis of RA must comprehensively investigate the role of the genes of the factors involved in the regulation of angiogenesis and inflammation, with particular emphasis on molecular genetic mechanisms for monitoring the baseline level of production of these regulatory factors.