VAV1 Gene Polymorphisms in Patients with Rheumatoid Arthritis

Abstract

Introduction: Rheumatoid arthritis (RA) is an important public health problem because this disease often causes disability. RA is a chronic, destructive autoimmune disease that leads to joint destruction and the development of extraarticular manifestations. VAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells and affects T cell development, proliferation and activation. The VAV1 gene contains 27 exons and is located on chromosome 19. In this study, we examined the association between VAV1 rs2546133 and rs2617822 polymorphisms and RA. Methods: We examined 422 patients with RA and 338 healthy subjects as the control group. Results: Among RA patients, there was a statistically significant increase in the frequency of VAV1 rs2546133 polymorphism in T allele carriers (TT + CT versus CC, odds ratio: 1.69, 95% confidence interval 1.05–2.73, p = 0.035). There was no statistically significant difference in the distribution of the rs2617822 genotypes and alleles between RA patients and the control group. Additionally, patients who carried the VAV1 rs2546133 T and rs2617822 G allele presented an increased frequency of extraarticular manifestations: vasculitis, amyloidosis and Sjogren syndrome. Conclusions: The results suggest an association between VAV1 gene rs2617822 polymorphism and RA.

The SELP, CD93, IL2RG, and VAV1 Genes Associated with Atherosclerosis May Be Potential Diagnostic Biomarkers for Psoriasis

“…It has general features of chronic inflammation, such as intimal lining hyperplasia, inflammatory cell influx, and neovascularization with RA and other arthritides. SELP, CD93, VAV1, and IL2RG can participate in the pathogenesis of RA by participating in cell adhesion, 11 inducing monocyte differentiation, 25 signal transduction, 39 and immune cell infiltration, 40 respectively. Psoriatic arthritis and RA share common physiological and pathological mechanisms and immune pathways.…”

Distinct Roles of Vav Family Members in Adaptive and Innate Immune Models of Arthritis

“…To our knowledge, this is the first study demonstrating that the elimination of a single Vav family member confers full protection against antigen-induced arthritis. This might be relevant in the context of human disease, since recent studies have revealed a possible link between a specific VAV1 SNP (rs2546133) and rheumatoid arthritis severity [ 10 , 11 ]. rs2546133 + patients also exhibit extra-articular manifestations such as amyloidosis, Sjogren syndrome and vasculitis [ 10 ].…”

“…This might be relevant in the context of human disease, since recent studies have revealed a possible link between a specific VAV1 SNP (rs2546133) and rheumatoid arthritis severity [ 10 , 11 ]. rs2546133 + patients also exhibit extra-articular manifestations such as amyloidosis, Sjogren syndrome and vasculitis [ 10 ]. Likewise, there is a correlation between four VAV1 SNPs (rs682626-rs2546133-rs2617822-rs12979659) and the development of a rheumatoid arthritis condition negative for antibodies to citrullinated circular peptides [ 11 ].…”

“…In line with this, a number of observations suggest that some Vav family members can also be connected to this disease. For example, recent studies have linked VAV1 single nucleotide polymorphisms (SNP) with the degree of severity of rheumatoid arthritis, multiple sclerosis and other autoimmune diseases [ 10 , 11 , 12 ]. SNPs found in the rat Vav1 locus have also been associated with the severity of autoimmune encephalomyelitis (the rat model for multiple sclerosis) and pristane-induced autoimmune arthritis [ 11 , 12 ].…”

One year in review 2021: pathogenesis of rheumatoid arthritis

“…The CTLA4 gene polymorphism rs11571319 was found to be associated with RA susceptibility in the Pakistani population (10). VAV1, an intracellular signal transduction protein, that plays an important role in development, proliferation and activation of T cells, was widely investigated and patients carrying VAV1 252546133T and 252617822G allele presented an increased frequency of extra-articular manifestations (11). Furthermore, several variants may contribute to disease susceptibility by regulating molecules involved in oxidative stress or bone homeostasis.…”