000			04273na a2200781 4500
999			_c2741 _d2741
003			PC2741
005			20190820134750.0
008			130622s2013 xxx||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_aCarreira Delgado, Patricia Esmeralda _9467 _eReumatología
245	0	4	_aThe systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis. _h[artículo]
260			_bPloS one, _c2013
300			_a8(1):e54419.
500			_aFormato Vancouver: Carmona FD, Martin JE, Beretta L, Simeón CP, Carreira PE, Callejas JL et al. Spanish Scleroderma Group. The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis. PLoS One. 2013;8(1):e54419.
501			_aPMID: 23372721
504			_aContiene 25 referencias
520			_aSystemic 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.
710			_9123 _aServicio de Reumatología
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553151/ _yAcceso libre
942			_n0 _2ddc _cART