OBJECTIVE: The STAT4 gene encodes a transcription factor involved in the signaling pathways of several cytokines, including interleukin-12 (IL-12), the type I interferons, and IL-23. Recently, the association of a STAT4 haplotype marked by rs7574865 with rheumatoid arthritis (RA) and systemic lupus erythematosus was reported. The aim of this study was to investigate the role of this STAT4 tagging polymorphism in other immune-mediated diseases. METHODS: The study group comprised 2,776 consecutively recruited Spanish individuals: 575 with RA, 440 with multiple sclerosis, 700 with inflammatory bowel disease, 311 with type 1 diabetes, and 723 ethnically matched healthy control subjects. The STAT4 polymorphism rs7574865 was genotyped using a predesigned TaqMan assay. Allele and genotype frequencies in patients and control subjects were compared by chi-square test. RESULTS: The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin (for T versus G, P = 1.2 x 10(-6), odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.31-1.92), and the association was described for the first time in both clinical forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis (for T versus G, P = 0.006, OR 1.29, 95% CI 1.07-1.55), and in type 1 diabetes mellitus (for T versus G, P = 0.008, OR 1.36, 95% CI 1.07-1.71). In contrast, the genotypic distribution of this polymorphism showed no difference between patients with multiple sclerosis and healthy control subjects (for T versus G, P = 0.83, OR 1.02, 95% CI 0.82-1.28). CONCLUSION: The STAT4 gene is emerging as a novel common risk factor for diverse complex diseases.
OBJECTIVE: The STAT4 gene encodes a transcription factor involved in the signaling pathways of several cytokines, including interleukin-12 (IL-12), the type I interferons, and IL-23. Recently, the association of a STAT4 haplotype marked by rs7574865 with rheumatoid arthritis (RA) and systemic lupus erythematosus was reported. The aim of this study was to investigate the role of this STAT4 tagging polymorphism in other immune-mediated diseases. METHODS: The study group comprised 2,776 consecutively recruited Spanish individuals: 575 with RA, 440 with multiple sclerosis, 700 with inflammatory bowel disease, 311 with type 1 diabetes, and 723 ethnically matched healthy control subjects. The STAT4 polymorphism rs7574865 was genotyped using a predesigned TaqMan assay. Allele and genotype frequencies in patients and control subjects were compared by chi-square test. RESULTS: The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin (for T versus G, P = 1.2 x 10(-6), odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.31-1.92), and the association was described for the first time in both clinical forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis (for T versus G, P = 0.006, OR 1.29, 95% CI 1.07-1.55), and in type 1 diabetes mellitus (for T versus G, P = 0.008, OR 1.36, 95% CI 1.07-1.71). In contrast, the genotypic distribution of this polymorphism showed no difference between patients with multiple sclerosis and healthy control subjects (for T versus G, P = 0.83, OR 1.02, 95% CI 0.82-1.28). CONCLUSION: The STAT4 gene is emerging as a novel common risk factor for diverse complex diseases.
Authors: Sampath Prahalad; Sterling Hansen; April Whiting; Stephen L Guthery; Bronte Clifford; Bernadette McNally; Andrew S Zeft; John F Bohnsack; Lynn B Jorde Journal: Arthritis Rheum Date: 2009-07
Authors: Ann W Morgan; James I Robinson; Philip G Conaghan; Stephen G Martin; Elizabeth M A Hensor; Michael D Morgan; Lori Steiner; Henry A Erlich; Hock-Chye Gooi; Anne Barton; Jane Worthington; Paul Emery Journal: Arthritis Res Ther Date: 2010-03-30 Impact factor: 5.156
Authors: Carlos Riveros; Drew Mellor; Kaushal S Gandhi; Fiona C McKay; Mathew B Cox; Regina Berretta; S Yahya Vaezpour; Mario Inostroza-Ponta; Simon A Broadley; Robert N Heard; Stephen Vucic; Graeme J Stewart; David W Williams; Rodney J Scott; Jeanette Lechner-Scott; David R Booth; Pablo Moscato Journal: PLoS One Date: 2010-12-01 Impact factor: 3.240
Authors: Jürgen Glas; Julia Seiderer; Melinda Nagy; Christoph Fries; Florian Beigel; Maria Weidinger; Simone Pfennig; Wolfram Klein; Jörg T Epplen; Peter Lohse; Matthias Folwaczny; Burkhard Göke; Thomas Ochsenkühn; Julia Diegelmann; Bertram Müller-Myhsok; Darina Roeske; Stephan Brand Journal: PLoS One Date: 2010-04-29 Impact factor: 3.240