RT Journal Article
T1 The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis
A1 Carmona, F David
A1 Martín, José-Ezequiel
A1 Beretta, Lorenzo
A1 Simeón, Carmen P
A1 Carreira, Patricia E
A1 Callejas, José Luis
A1 Fernández-Castro, Mónica
A1 Sáez-Comet, Luis
A1 Beltrán, Emma
A1 Camps, María Teresa
A1 Egurbide, María Victoria
A1 Airó, Paolo
A1 Scorza, Raffaella
A1 Lunardi, Claudio
A1 Hunzelmann, Nicolas
A1 Riemekasten, Gabriela
A1 Witte, Torsten
A1 Kreuter, Alexander
A1 Distler, Jörg H W
A1 Madhok, Rajan
A1 Shiels, Paul
A1 van Laar, Jacob M
A1 Fonseca, Carmen
A1 Denton, Christopher
A1 Herrick, Ariane
A1 Worthington, Jane
A1 Schuerwegh, Annemie J
A1 Vonk, Madelon C
A1 Voskuyl, Alexandre E
A1 Radstake, Timothy R D J
A1 Martín, Javier
K1 Factores reguladores del interferón
K1 Predisposición genética a la enfermedad
K1 Haplotipos
K1 Polimorfismo de nucleótido simple
K1 Lupus eritematoso sistémico
K1 Desequilibrio de ligamiento
K1 Grupo de ascendencia continental europea
K1 Factores de riesgo
AB Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10(-8), OR  = 1.22, CI 95%  = 1.14-1.30; rs2004640: P  = 4.60×10(-7), OR  = 0.84, CI 95%  = 0.78-0.90; rs10488631: P  = 7.53×10(-20), OR  = 1.63, CI 95%  = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10(-22), OR  = 1.75, CI 95%  = 1.56-1.97) better explained the observed association (likelihood P-value  = 1.48×10(-4)), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.
PB Public Library of Science
YR 2013
FD 2013-08
LK http://hdl.handle.net/10668/1942
UL http://hdl.handle.net/10668/1942
LA en
NO Carmona FD, Martín JE, Beretta L, Simeón CP, Carreira PE, Callejas JL, et al. The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis. PLoS ONE. 2013; 8(1):e54419
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 10, 2025