title: The ITGAV-rs3911238 polymorphism is associated with disease activity in rheumatoid arthritis.
abstract: 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-αv 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 ITGAV-rs3911238 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.
authors.affiliation: Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran. avaisiraygani@gmail.com.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Shakiba
authors.affiliation: Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran. tavilani@gmail.com.
authors.forename: Haidar
authors.initials: H
authors.lastname: Tavilani
authors.affiliation: Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran. mtgoodarzi@yahoo.com.
authors.forename: Mohamad Taghi
authors.initials: MT
authors.lastname: Goodarzi
authors.affiliation: Department of Toxicology and pharmacology, Kermanshah University of Medical Sciences, and Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. amir1kiani@yahoo.com.
authors.forename: Amir
authors.initials: A
authors.lastname: Kiani
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, U.S.A. tpourmotabbe@gmail.com.
authors.forename: Tayehbbeh
authors.initials: T
authors.lastname: Pourmotabbed
authors.affiliation: Molecular Diagnostic Research Center, AND Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran. asadvaisiraygani@kums.ac.ir.
authors.forename: Asad
authors.initials: A
authors.lastname: Vaisi-Raygani
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D039564:Integrin alphaV / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010456:Peptides, Cyclic / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D018836:Inflammation Mediators; D039564:Integrin alphaV; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein