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SAT0016 Functional variant in the IFNG gene predisposes to cardiovascular risk in rheumatoid arthritis patients
  1. M. García-Bermúdez1,
  2. C. González-Juanatey2,
  3. G. Robledo1,
  4. R. Lόpez-Mejías3,
  5. R. Blanco3,
  6. S. Castañeda4,
  7. J.A. Miranda-Filloy5,
  8. B. Fernández-Gutiérrez6,
  9. A. Balsa7,
  10. I. González-Alvaro4,
  11. C. Gόmez-Vaquero8,
  12. J. Llorca9,
  13. J. Martin1,
  14. M.A. González-Gay3
  1. 1Inmunology and Cell Biology, Instituto de Parasitología y Biomedicina Lόpez-Neyra, Ipbln-Csic, Granada
  2. 2Cardiology, Hospital Xeral-Calde, Lugo
  3. 3Rheumatology, Hospital Universitario Marqués de Valdecilla, Ifimav, Santander
  4. 4Rheumatology, Hospital Universitario la Princesa, IIS-Princesa, Madrid
  5. 5Rheumatology, Hospital Xeral-Calde, Lugo
  6. 6Rheumatology, Hospital Clinico San Carlos
  7. 7Rheumatology, Hospital Universitario La Paz, Madrid
  8. 8Rheumatology, Hospital Universitario Bellvitge, Barcelona
  9. 9Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), Ifimav, Santander, Spain


Background Rheumatoid 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).

Objectives In this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in RA patients.

Methods 1406 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.

Results Adjusted 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.

Conclusions IFNG rs2430561 (+874A/T) gene functional variant may influence the development of CV disease in patients with RA.

Acknowledgements Supported 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).

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Disclosure of Interest None Declared

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