000			02893na a2200229 4500
003			H12O
005			20180113071803.0
008			130622s2011 xxx||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_9467 _aCarreira Delgado, Patricia Esmeralda _eReumatología
245	0	0	_aIdentification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy _h[artículo]
260			_bPLoS Genetics, _c2011.
300			_a7(7):e1002178.
500			_aFormato Vancouver: Gorlova O, Martin JE, Rueda B, Koeleman BP, Ying J, Teruel M, et al. Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy. PLoS Genet. 2011;7(7):e1002178.
501			_aPMID: 21779181
504			_aContiene 51 referencias
520			_aThe aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39×10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84×10(-21), OR = 0.55) and ATA (P = 1.14×10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
710			_9123 _aServicio de Reumatología
856			_uhttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002178 _yAcceso libre
942			_n0 _2ddc _cART
999			_c9392 _d9392