title: Interferon regulatory factor 5 genetic variants are associated with cardiovascular disease in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease risk. Interferon regulatory factor 5 (IRF5) is a regulator of type I interferon induction. Recently, researchers have described an association between multiple single-nucleotide polymorphisms of the IRF5 gene and some rheumatic disorders. In this study, we aimed to evaluate whether three different haplotype blocks within the IRF5 locus which have been shown to alter the protein function are involved in the risk of CV events occurring in Spanish RA patients.
  
  
  METHODS
  Three IRF5 polymorphisms (rs2004640, rs2070197 and rs10954213) representative of each haplotype group were genotyped by performing TaqMan assays using a 7900HT Fast Real-Time PCR System with tissue from a total of 2,137 Spanish patients diagnosed with RA. Among them, 390 (18.2%) had experienced CV events. The relationship of IRF5 genotypes and haplotypes to CV events was tested using Cox regression.
  
  
  RESULTS
  Male sex, age at RA diagnosis and most traditional risk factors (hypertension, dyslipidemia and smoking habit) were associated with increased risk for CV events in the RA population. Interestingly, a protective effect of both IRF5 rs2004640 GG and IRF5 rs10954213 GG genotypes against the risk for CV events after adjusting the results for sex, age at RA diagnosis and traditional CV disease risk factors was observed (hazard ratio (HR) = 0.6, 95% confidence interval (CI) = 0.38 to 0.92, P = 0.02; and HR = 0.58, 95% CI = 0.36 to 0.95, P = 0.03, respectively). Moreover, we detected a protective effect of the GTG haplotype against the risk for CV events after adjusting the results for potential confounding factors (HR = 0.72, 95% CI = 0.56 to 0.93, P = 0.012).
  
  
  CONCLUSIONS
  Our results reveal that IRF5 gene variants are associated with risk of CV events in patients with RA.
authors.forename: Mercedes
authors.initials: M
authors.lastname: García-Bermúdez
authors.forename: Raquel
authors.initials: R
authors.lastname: López-Mejías
authors.forename: Fernanda
authors.initials: F
authors.lastname: Genre
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Carlos
authors.initials: C
authors.lastname: González-Juanatey
authors.forename: Alfonso
authors.initials: A
authors.lastname: Corrales
authors.forename: Begoña
authors.initials: B
authors.lastname: Ubilla
authors.forename: José A
authors.initials: JA
authors.lastname: Miranda-Filloy
authors.forename: Trinitario
authors.initials: T
authors.lastname: Pina
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Vaquero
authors.forename: Luis
authors.initials: L
authors.lastname: Rodríguez-Rodríguez
authors.forename: Benjamín
authors.initials: B
authors.lastname: Fernández-Gutiérrez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Longo
authors.forename: Patricia
authors.initials: P
authors.lastname: Carreira
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
mesh_terms: D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors