Analysis of the interferon gamma (rs2430561, +874T/A) functional gene variant in relation to the presence of cardiovascular events in rheumatoid arthritis

PLoS One. 2012;7(10):e47166. doi: 10.1371/journal.pone.0047166. Epub 2012 Oct 15.


Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA.

Methods: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. 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 rs2430561 allele 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 carotid artery intima-media thickness (IMT) (n = 286) and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA.

Results: Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not.

Conclusion: Our results do not support a role of IFNG rs2430561 (+874T/A) functional gene variant in the development of CV disease in RA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / genetics*
  • Atherosclerosis / etiology
  • Atherosclerosis / genetics
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors


  • Interferon-gamma

Grant support

This work was supported by two grants from Fondo de Investigaciones Sanitarias PI06-0024 and PS09/00748 (Spanish National Health System; Ministry of Science and Innovation, Spain Government) and by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), National Health System (Spain) within the VI Programa Nacionalde I+D+i 2008–2011 (FEDER). This work was supported in part by grants from the EuropeanIMI BTCure Program. MGB is a beneficiary of a grant from Fundación Española de Reumatología. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.