Functional Variant In The Ifng Gene Predisposes To Cardiovascular Risk In Rheumatoid Arthritis Patients

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease associated with high risk of cardiovascular (CV) disease (1). Besides classic CV risk factors, “high-grade” systemic inflammation and immune dysregulation play a crucial role in the development of accelerated atherosclerosis observed in RA (2-5). IFN-γ is a pleiotropic soluble cytokine with antiviral and anti-tumor properties. This cytokine is found in RA patients’ synovium and synovial fluid (6), and polymorphisms within its gene sequence may be biologically plausible candidates for influencing the incidence and severity of RA (7).ObjectivesIn this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in RA patients.Methods1406 patientsfulfilling the 1987 ACR classification criteria for RA were genotyped for the IFNG (rs2430561, +874A/T) polymorphism by ARMS-PCR method followed by gel electrophoresis analysis. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine endothelial function (Flow-Mediated endothelium-dependent, FMD) (n=128) and carotid artery intima-media thickness (IMT) (n=108), respectively.ResultsAdjusted logistic regression model disclosed that presence of the minor allele T was associated with increased risk of suffering CV events in RA patients (p=0.022, OR 1.63 [95% CI 1.07-2.49]). This increased risk was also observed in the subgroup of patients with heart failure (p=0.025, OR 2.45 [95% CI 1.12-5.37]). Also, higher carotid IMT and lower FMD values were found in RA patients carrying IFNG rs2430561 variant allele T, although differences did not achieve statistical significance.ConclusionsIFNG rs2430561 (+874A/T) gene functional variant may influence the development of CV disease in patients with RA.AcknowledgementsSupported by two grants from Fondo de Investigaciones Sanitarias PI06-0024 and PS09/00748 (Spain). This work was partially supported by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+i 2008-2011 (FEDER). MGB is a recipient of a grant from Fundaciόn Española de Reumatología (FER).ReferencesKitas GD, Gabriel SE. Ann Rheum Dis 2011;70(1):8-14. Dessein PH, Joffe BI, Veller MG, et al. J Rheumatol 2005;32(3):435-42. Libby P. Am J Med 2008;121(10 Suppl 1):S21-31. González-Gay MA, González-Juanatey C, Lόpez-Diaz MJ, et al. Arthritis Rheum 2007;57(1):125-32. Kramer HR, Giles JT. Arthritis Care Res (Hoboken) 2011;63(4):484-99. Baccala R, Kono DH, Theofilopoulos AN. Immunol Rev 2005;204:9-26. Pokorny V, McLean L, McQueen F, Abu-Maree M, Yeoman S. Lancet 2001;358(9276):122-3.Disclosure of InterestNone Declared