Dataset Information

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

ABSTRACT:

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-?) 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-? 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.

SUBMITTER: Garcia-Bermudez M

PROVIDER: S-EPMC3471910 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

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

García-Bermúdez Mercedes M López-Mejías Raquel R González-Juanatey Carlos C Corrales Alfonso A Robledo Gema G Castañeda Santos S Miranda-Filloy José A JA Blanco Ricardo R Fernández-Gutiérrez Benjamín B Balsa Alejandro A González-Alvaro Isidoro I Gómez-Vaquero Carmen C Llorca Javier J Martín Javier J González-Gay Miguel A MA

PloS one 20121015 10

<h4>Objective</h4>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.<h4>Methods</h4>One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA ...[more]

PMID: 23077565

Similar Datasets

Project description:ObjectiveFindings from recent transcriptome analyses of the synovium of patients with rheumatoid arthritis (RA) have revealed that 15-fold expanded HLA-DR+CD90+ synovial fibroblasts potentially act as key mediators of inflammation. The reasons for the expansion of HLA-DR+CD90+ synovial fibroblasts are unclear, but genetic signatures indicate that interferon-γ (IFNγ) plays a central role in the generation of this fibroblast subset. The present study was undertaken to investigate the generation, function and therapeutically intended blockage of HLA-DR+CD90+ synovial fibroblasts.MethodsWe combined functional assays using primary human materials and focused bioinformatic analyses of mass cytometry and transcriptomics patient data sets.ResultsWe detected enriched and activated Fcγ receptor type IIIa-positive (CD16+) NK cells in the synovial tissue from patients with active RA. Soluble immune complexes were recognized by CD16 in a newly described reporter cell model, a mechanism that could be contributing to the activation of natural killer (NK) cells in RA. In vitro, NK cell-derived IFNγ induced HLA-DR on CD90+ synovial fibroblasts, leading to an inflammatory, cytokine-secreting HLA-DR+CD90+ phenotype. HLA-DR+CD90+ synovial fibroblasts consecutively activated CD4+ T cells upon receptor crosslinking via superantigens. HLA-DR+CD90+ synovial fibroblasts also activated CD4+ T cells in the absence of superantigens, an effect that was initiated by NK cell-derived IFNγ and that was 4 times stronger in patients with RA compared to patients with osteoarthritis. Finally, JAK inhibition in synovial fibroblasts prevented HLA-DR induction and blocked proinflammatory signals to T cells.ConclusionThe HLA-DR+CD90+ phenotype represents an activation state of synovial fibroblasts during the process of inflammation in RA that can be induced by IFNγ, likely generated from infiltrating leukocytes such as activated NK cells. The induction of these proinflammatory, interleukin-6-producing, and likely antigen-presenting synovial fibroblasts can be targeted by JAK inhibition.

Dataset Information

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

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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