PMID- 23372721
OWN - NLM
STAT- MEDLINE
DCOM- 20130722
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 1
DP  - 2013
TI  - The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic 
      sclerosis.
PG  - e54419
LID - 10.1371/journal.pone.0054419 [doi]
LID - e54419
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  = 1.34x10(-8), OR  = 1.22, CI 95%  = 1.14-1.30; 
      rs2004640: P  = 4.60x10(-7), OR  = 0.84, CI 95%  = 0.78-0.90; rs10488631: P 
       = 7.53x10(-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 
       = 9.04x10(-22), OR  = 1.75, CI 95%  = 1.56-1.97) better explained the observed 
      association (likelihood P-value  = 1.48x10(-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.
FAU - Carmona, F David
AU  - Carmona FD
AD  - Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada, Spain. 
      dcarmona@ipb.csic.es
FAU - Martin, Jose-Ezequiel
AU  - Martin JE
FAU - Beretta, Lorenzo
AU  - Beretta L
FAU - Simeon, Carmen P
AU  - Simeon CP
FAU - Carreira, Patricia E
AU  - Carreira PE
FAU - Callejas, Jose Luis
AU  - Callejas JL
FAU - Fernandez-Castro, Monica
AU  - Fernandez-Castro M
FAU - Saez-Comet, Luis
AU  - Saez-Comet L
FAU - Beltran, Emma
AU  - Beltran E
FAU - Camps, Maria Teresa
AU  - Camps MT
FAU - Egurbide, Maria Victoria
AU  - Egurbide MV
CN  - Spanish Scleroderma Group
FAU - Airo, Paolo
AU  - Airo P
FAU - Scorza, Raffaella
AU  - Scorza R
FAU - Lunardi, Claudio
AU  - Lunardi C
FAU - Hunzelmann, Nicolas
AU  - Hunzelmann N
FAU - Riemekasten, Gabriela
AU  - Riemekasten G
FAU - Witte, Torsten
AU  - Witte T
FAU - Kreuter, Alexander
AU  - Kreuter A
FAU - Distler, Jorg H W
AU  - Distler JH
FAU - Madhok, Rajan
AU  - Madhok R
FAU - Shiels, Paul
AU  - Shiels P
FAU - van Laar, Jacob M
AU  - van Laar JM
FAU - Fonseca, Carmen
AU  - Fonseca C
FAU - Denton, Christopher
AU  - Denton C
FAU - Herrick, Ariane
AU  - Herrick A
FAU - Worthington, Jane
AU  - Worthington J
FAU - Schuerwegh, Annemie J
AU  - Schuerwegh AJ
FAU - Vonk, Madelon C
AU  - Vonk MC
FAU - Voskuyl, Alexandre E
AU  - Voskuyl AE
FAU - Radstake, Timothy R D J
AU  - Radstake TR
FAU - Martin, Javier
AU  - Martin J
LA  - eng
GR  - 17552/ARC_/Arthritis Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130123
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (IRF5 protein, human)
RN  - 0 (Interferon Regulatory Factors)
SB  - IM
MH  - Alleles
MH  - Female
MH  - Gene Frequency
MH  - Genetic Loci
MH  - *Genetic Predisposition to Disease
MH  - *Haplotypes
MH  - Humans
MH  - Interferon Regulatory Factors/*genetics
MH  - Linkage Disequilibrium
MH  - Lupus Erythematosus, Systemic/complications/ethnology/*genetics
MH  - Male
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - Scleroderma, Systemic/complications/ethnology/*genetics
MH  - White People
PMC - PMC3553151
COIS- Competing Interests: The authors have declared that no competing interests exist.
FIR - Ortego-Centeno, Norberto
IR  - Ortego-Centeno N
FIR - Rios, Raquel
IR  - Rios R
FIR - Navarrete, Nuria
IR  - Navarrete N
FIR - Portales, Rosa Garcia
IR  - Portales RG
FIR - Fernandez-Nebro, Antonio
IR  - Fernandez-Nebro A
FIR - Gonzalez-Escribano, Maria F
IR  - Gonzalez-Escribano MF
FIR - Sanchez-Roman, Julio
IR  - Sanchez-Roman J
FIR - Garcia-Hernandez, Francisco Jose
IR  - Garcia-Hernandez FJ
FIR - Castillo, Maria Jesus
IR  - Castillo MJ
FIR - Aguirre, Maria Angeles
IR  - Aguirre MA
FIR - Gomez-Gracia, Inmaculada
IR  - Gomez-Gracia I
FIR - Fernandez-Gutierrez, Benjamin
IR  - Fernandez-Gutierrez B
FIR - Rodriguez-Rodriguez, Luis
IR  - Rodriguez-Rodriguez L
FIR - Vicente, Esther
IR  - Vicente E
FIR - Andreu, Jose Luis
IR  - Andreu JL
FIR - de la Pena, Paloma Garcia
IR  - de la Pena PG
FIR - Lopez-Longo, Francisco Javier
IR  - Lopez-Longo FJ
FIR - Martinez, Lina
IR  - Martinez L
FIR - Fonollosa, Vicente
IR  - Fonollosa V
FIR - Espinosa, Gerard
IR  - Espinosa G
FIR - Castellvi, Ivan
IR  - Castellvi I
FIR - Tolosa, Carlos
IR  - Tolosa C
FIR - Pros, Anna
IR  - Pros A
FIR - Carballeira, Monica Rodriguez
IR  - Carballeira MR
FIR - Narvaez, Francisco Javier
IR  - Narvaez FJ
FIR - Gonzalez-Gay, Miguel Angel
IR  - Gonzalez-Gay MA
FIR - Diaz, Bernardino
IR  - Diaz B
FIR - Trapiella, Luis
IR  - Trapiella L
FIR - Gallego, Maria
IR  - Gallego M
FIR - Freire, Maria del Carmen
IR  - Freire Mdel C
FIR - Vaqueiro, Ines
IR  - Vaqueiro I
FIR - Diaz, Federico
IR  - Diaz F
FIR - Hernandez, Vanesa
IR  - Hernandez V
FIR - Roman-Ivorra, Jose Andres
IR  - Roman-Ivorra JA
FIR - Garcia, Francisco J Blanco
IR  - Garcia FJ
FIR - Oreiro, Natividad
IR  - Oreiro N
EDAT- 2013/02/02 06:00
MHDA- 2013/07/23 06:00
PMCR- 2013/01/23
CRDT- 2013/02/02 06:00
PHST- 2012/09/05 00:00 [received]
PHST- 2012/12/11 00:00 [accepted]
PHST- 2013/02/02 06:00 [entrez]
PHST- 2013/02/02 06:00 [pubmed]
PHST- 2013/07/23 06:00 [medline]
PHST- 2013/01/23 00:00 [pmc-release]
AID - PONE-D-12-26885 [pii]
AID - 10.1371/journal.pone.0054419 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(1):e54419. doi: 10.1371/journal.pone.0054419. Epub 2013 Jan 23.