Supported in part by funds from the European Union FEDER, the Fondo de Investigación Sanitaria (grants PI12/00523 and PI12/00060 from the Instituto de Salud Carlos III, Spanish Ministry of Health), and a RETICS program grant (RD12/0009 from the Instituto de Salud Carlos III, Spanish Ministry of Health). Dr. Rodríguez-Carrio's work was supported by an FPU fellowship from the Spanish Ministry of Education (AP2010-1614). Dr. López-Mejías is recipient of a Sara Borrell postdoctoral fellowship from the Instituto de Salud Carlos III at the Spanish Ministry of Health (CD12/00425).
This work was supported by the European Union FEDER funds and 'Fondo de Investigación Sanitaria' (ISCIII, Health Ministry, Spain) ´ [grant numbers PI12/00523, PI12/00060 and PI15/00525]; the RETICS Programs (ISCIII, Health Ministry, Spain) [grant number RD12/0009 (RIER)]; the Spanish Society for Rheumatology (SER) [grant number xxx]; the FICYT (Fundación para el fomento en Asturias de la Investigación Científica aplicada y la Tecnología) [grant number GRUPIN14-043 (to J.R.-C.)]; and the RETICS Program (RIER) [grant number RD12/0009/0013 (to R.L.M.)].
This work was supported by European Union FEDER funds, "Fondo de Investigación Sanitaria (FIS, PI12/00523 and PI16/00113; ISCIII, Spain) and SER/FER funds (Sociedad Española de Reumatología, FER043/2016). J.R.-C. is supported by a postdoctoral contract from the "Juan de la Cierva" program (FJCI-2015-23849; MINECO, Spain).
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 ; 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
Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Since CD40-CD154 binding has direct consequences on inflammation process initiation, we aimed to replicate previous findings related to disease susceptibility in Spanish RA population. Furthermore, as the major complication in RA disease patients is the development of CV events due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are present in patients with acute myocardial infarction, we assessed the potential association of CD40 and CD154/CD40L gene variants with CV risk in Spanish RA patients. Methods: One thousand five hundred and seventy-five patients fulfilling the 1987 ACR classification criteria for RA and 1600 matched controls were genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide polymorphism genotyping assays. Afterwards, we investigated the influence of CD40-CD154 gene variants in the development of CV events. Also, in a subgroup of 273 patients without history of CV events, we assessed the influence of these polymorphisms in the risk of subclinical atherosclerosis determined by carotid ultrasonography. Results: Nominally significant differences in the allele frequencies for the rs1883832 CD40 gene polymorphism between RA patients and controls were found (p = 0.038). Although we did not observe a significant association of CD40-CD154 gene variants with the development of CV events, an ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment, follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide antibodies disclosed a significant association (p = 0.0047) between CD40 rs1535045 polymorphism and carotid intima media thickness, a surrogate marker of atherosclerosis. Conclusion: Data from our pilot study indicate a potential association of rs1883832 CD40 gene polymorphism with susceptibility to RA. Also, the CD40 rs1535045 gene variant may influence development of subclinical atherosclerosis in RA patients ; 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 Nacional de I+D+i 2008–2011 (FEDER). This work was supported in part by grants from the European IMI BTCure Program. MGB is a beneficiary of a grant from Fundación Española de Reumatología.
