The ITGAV-rs3911238 Polymorphism Is Associated with Disease Activity in Rheumatoid Arthritis

Evidences indicate that angiogenesis is an important process in the development of destructive synovial tissue in rheumatoid arthritis (RA). Recently, it has been shown that the polymorphism of the integrin-v subunit encoded by the ITGAV gene plays a role in angiogenesis and is considered as RA susceptibility loci. This study investigated association of four single nucleotide polymorphisms (SNPs) in ITGAV with disease activity score (DAS28), serum levels of C-reactive protein (CRP), and anti-cyclic citrullinated peptide(anti-CCP) antibody in 419 RA patients and 398 healthy individuals. Four SNPs in ITGAV gene (rs3911238, rs3738919, rs10174098 and rs3768777) were analyzed. Serum concentrations of anti-CCP antibody and CRP were measured by ELISA. We used the EULAR activity criteria to calculate DAS28-CRP. Among these SNPs, the ITGAV-rs3911238-G/C polymorphism was associated with RA disease activity [remission-to-low and moderate-to-high in codominant model (CC vs.GG: OR=1.53, p=0.041 and allele (C vs. G: OR=1.18, p=0.042)] and presence of anti-CCP (codominant CC vs.GG: OR=2.77, p=0.001, allele C vs. G: OR=1.19,p=0.033). The carriers of CC genotype ITGAVrs3911238 had higher serum levels of CRP and anti-CCP antibody titer and higher ESR and disease activity score than carriers of GG and CG genotypes. Furthermore, haplotypes analysis showed that ITGAV rs3733891C/rs3768777T/rs3911238C/rs10174098A and ITGAV rs3733891A/rs3768777T/rs3911238G/rs10174098A haplotypes increased severity and anti-CCP antibody in RA patients (OR=5.54, p=0.049 and OR=2.89; p=0.024, respectively) in comparison with ITGAV rs3733891C/rs3768777T/rs3911238G/rs10174098A haplotypes. Thus, the present study demonstrated that the link between systemic inflammatory markers and the ITGAV-rs3911238 polymorphism allele in Iranian RA patients.