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Title

STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility

AuthorsCénit, M. C.; Alcina, Antonio; Márquez, Ana; Mendoza, Juan L.; Díaz-Rubio, M.; Heras, Virginia de las; Izquierdo, Guillermo; Arroyo, R.; Fernández, Óscar; Concha, Emilio G. de la; Matesanz, F.; Urcelay, Elena
Issue Date2010
PublisherNature Publishing Group
CitationGenes and Immunity 11(3): 264- 268 (2010)
AbstractSTAT3 (signal transducer and activator of transcription 3) signaling is a critical component of Th17-dependent autoimmune processes. Genome-wide association studies (GWAS) have revealed the role of the STAT3 gene in inflammatory bowel disease (IBD) susceptibility, although confirmation in clinical subphenotypes is warranted. Mice with targeted deletion of Stat3 in T cells are resistant to experimental autoimmune encephalomyelitis, which is a multiple sclerosis (MS) model. Moreover, increased phosphorylated STAT3 was reported in T cells of patients evolving from clinically isolated syndrome to defined MS and in relapsing patients. These evidences led us to analyze the role of STAT3 in Crohn's disease (CD), ulcerative colitis (UC) and MS risk. Polymorphisms in the STAT3 region (rs3809758/rs744166/rs1026916/rs12948909) were genotyped and the inferred haplotypes were subsequently analyzed in 860 IBD and 1540 MS Spanish patients and 1720 ethnically matched controls. The haplotype conformed by the risk alleles of each polymorphism was significantly associated with both clinical phenotypes of IBD (CD: P0.005, odds ratio 1.25, 95% confidence interval 1.06-1.46; and UC: P0.002, odds ratio 1.19, 95% confidence interval 1.02-1.38). No evidence of association was detected for MS. The originally described association of IBD with STAT3 polymorphisms is corroborated for the two clinical phenotypes, CD and UC, in an independent population. A major role of this gene in MS seems unlikely. © 2010 Macmillan Publishers Limited All rights reserved.
URIhttp://hdl.handle.net/10261/57841
DOI10.1038/gene.2010.10
Identifiersdoi: 10.1038/gene.2010.10
issn: 1466-4879
e-issn: 1476-5470
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