STAT4

Summary

Gene Symbol: STAT4
Description: signal transducer and activator of transcription 4
Alias: SLEB11, signal transducer and activator of transcription 4, signal transducer and activator of transcription 4 variant 3
Species: human
Products:     STAT4

Top Publications

  1. Taylor K, Remmers E, Lee A, Ortmann W, Plenge R, Tian C, et al. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus. PLoS Genet. 2008;4:e1000084 pubmed publisher
    ..A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes ..
  2. Remmers E, Plenge R, Lee A, Graham R, Hom G, Behrens T, et al. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med. 2007;357:977-86 pubmed
    ..We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North ..
  3. Su Y, Zhao Y, Liu X, Guo J, Jiang Q, Liu X, et al. Variation in STAT4 is associated with systemic lupus erythematosus in Chinese Northern Han population. Chin Med J (Engl). 2010;123:3173-7 pubmed
    Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations...
  4. Tsuchiya N, Kawasaki A, Hasegawa M, Fujimoto M, Takehara K, Kawaguchi Y, et al. Association of STAT4 polymorphism with systemic sclerosis in a Japanese population. Ann Rheum Dis. 2009;68:1375-6 pubmed publisher
  5. Pykäläinen M, Kinos R, Valkonen S, Rydman P, Kilpeläinen M, Laitinen L, et al. Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes. J Allergy Clin Immunol. 2005;115:80-7 pubmed
    ..The transcription factors STAT6, GATA3, and STAT4 mediate the cytokine-induced development of naive CD4 + T cells into either T H 1 or T H 2 type...
  6. Zhao Y, Liu X, Liu X, Su Y, Li Y, Zhang X, et al. Association of STAT4 gene polymorphism with increased susceptibility of rheumatoid arthritis in a northern Chinese Han subpopulation. Int J Rheum Dis. 2013;16:178-84 pubmed publisher
    Several studies have reported STAT4 polymorphism is strongly associated with increased susceptibility to rheumatoid arthritis (RA)...
  7. Zervou M, Goulielmos G, Castro Giner F, Tosca A, Krueger Krasagakis S. STAT4 gene polymorphism is associated with psoriasis in the genetically homogeneous population of Crete, Greece. Hum Immunol. 2009;70:738-41 pubmed publisher
    ..consideration that different autoimmune diseases may share some common pathogenetic pathways, we hypothesized that STAT4, a susceptibility gene found to be associated with increased risk for systemic lupus erythematosus, rheumatoid ..
  8. Thierfelder W, van Deursen J, Yamamoto K, Tripp R, Sarawar S, Carson R, et al. Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature. 1996;382:171-4 pubmed
    ..b>Stat4 was initially cloned as a result of its homology with Stat1 (refs 4, 5) and is widely expressed, although it is ..
  9. Kobayashi S, Ikari K, Kaneko H, Kochi Y, Yamamoto K, Shimane K, et al. Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population. Arthritis Rheum. 2008;58:1940-6 pubmed publisher
    b>STAT4 encodes a transcriptional factor that transmits signals induced by several key cytokines, and it might be a key molecule in the development of autoimmune diseases...

More Information

Publications85

  1. Korman B, Alba M, Le J, Alevizos I, Smith J, Nikolov N, et al. Variant form of STAT4 is associated with primary Sjögren's syndrome. Genes Immun. 2008;9:267-70 pubmed publisher
    Single nucleotide polymorphisms in the STAT4 gene have recently been shown to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)...
  2. Nordmark G, Kristjansdottir G, Theander E, Eriksson P, Brun J, Wang C, et al. Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrome. Genes Immun. 2009;10:68-76 pubmed publisher
    ..Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS...
  3. Zervou M, Mamoulakis D, Panierakis C, Boumpas D, Goulielmos G. STAT4: a risk factor for type 1 diabetes?. Hum Immunol. 2008;69:647-50 pubmed publisher
    ..b>STAT4, a transcription factor transmitting signals induced by several key cytokines, has recently been identified as a ..
  4. Seddighzadeh M, Gonzalez A, Ding B, Ferreiro Iglesias A, Gomez Reino J, Klareskog L, et al. Variants within STAT genes reveal association with anticitrullinated protein antibody-negative rheumatoid arthritis in 2 European populations. J Rheumatol. 2012;39:1509-16 pubmed publisher
    ..We investigated the association of STAT3 and STAT4 polymorphisms with serologically distinct subgroups of rheumatoid arthritis (RA)...
  5. Namjou B, Sestak A, Armstrong D, Zidovetzki R, Kelly J, Jacob N, et al. High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups. Arthritis Rheum. 2009;60:1085-95 pubmed publisher
    ..Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large ..
  6. Kariuki S, Kirou K, MacDermott E, Barillas Arias L, Crow M, Niewold T. Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo. J Immunol. 2009;182:34-8 pubmed
    Increased IFN-alpha signaling is a primary pathogenic factor in systemic lupus erythematosus (SLE). STAT4 is a transcription factor that is activated by IFN-alpha signaling, and genetic variation of STAT4 has been associated with risk of ..
  7. Park Y, Lee H, Park Y, Min D, Yang S, Kim D, et al. Evidence for the role of STAT4 as a general autoimmunity locus in the Korean population. Diabetes Metab Res Rev. 2011;27:867-71 pubmed publisher
    Recently, the association of a common STAT4 haplotype with type 1 diabetes (T1D) as well as rheumatoid arthritis has been documented in Caucasians and Koreans...
  8. Shen L, Liu R, Zhang H, Huang Y, Sun R, Tang P. Replication study of STAT4 rs7574865 G/T polymorphism and risk of rheumatoid arthritis in a Chinese population. Gene. 2013;526:259-64 pubmed publisher
    ..b>Signal transducer and activator of transcription 4 (STAT4) transmits signals induced by interleukin-12, interleukin-23 and interferon-?, which ..
  9. Lee Y, Woo J, Choi S, Ji J, Song G. Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis: a meta-analysis. Rheumatol Int. 2010;30:661-6 pubmed publisher
    The aim of this study was to determine whether the rs7574865 polymorphism of STAT4 (signal transducers and activators of transcription 4) confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities...
  10. Lee Y, Bae S, Choi S, Ji J, Song G. Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis. Mol Biol Rep. 2012;39:10627-35 pubmed publisher
    ..36E-22). In the non-HLA region, meta-analysis identified 6 SNPs associated with SLE with genome-wide significance (STAT4, TNPO3, BLK, FAM167A, and IRF5)...
  11. Harley J, Alarcon Riquelme M, Criswell L, Jacob C, Kimberly R, Moser K, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008;40:204-10 pubmed publisher
    ..3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < ..
  12. Kim E, Kim S, Moon C, Park J, Kim T, Kim W, et al. Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population. Life Sci. 2012;90:740-6 pubmed publisher
    ..We therefore performed a study to evaluate whether IL17A, IL23R, and STAT4 polymorphisms are associated with susceptibility to intestinal BD in the Korean population...
  13. Svenungsson E, Gustafsson J, Leonard D, Sandling J, Gunnarsson I, Nordmark G, et al. A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus. Ann Rheum Dis. 2010;69:834-40 pubmed publisher
    ..allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/..
  14. Yao B, Niu P, Surowy C, Faltynek C. Direct interaction of STAT4 with the IL-12 receptor. Arch Biochem Biophys. 1999;368:147-55 pubmed
    Signal transduction by interleukin-12 (IL-12) requires phosphorylation and activation of STAT4. Direct interaction of the SH2 domain of STAT4 with a phosphotyrosine residue in the IL-12 receptor has been proposed to be required for the ..
  15. Piotrowski P, Lianeri M, Wudarski M, Olesinska M, Jagodziński P. Contribution of STAT4 gene single-nucleotide polymorphism to systemic lupus erythematosus in the Polish population. Mol Biol Rep. 2012;39:8861-6 pubmed publisher
    The STAT4 has been found to be a susceptible gene in the development of systemic lupus erythematosus (SLE) in various populations...
  16. Bi C, Li B, Cheng Z, Hu Y, Fang Z, Zhai A. Association study of STAT4 polymorphisms and type 1 diabetes in Northeastern Chinese Han population. Tissue Antigens. 2013;81:137-40 pubmed publisher
    ..The signal transducer and activator of transcription 4 (STAT4) gene is one of the most interesting genes for the pathogenesis of autoimmune ..
  17. Yin H, Borghi M, Delgado Vega A, Tincani A, Meroni P, Alarcon Riquelme M. Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome. Arthritis Rheum. 2009;60:2468-71 pubmed publisher
    ..We genotyped 3 single-nucleotide polymorphisms (SNPs) in IRF5 (rs2004640, rs2070197, and rs10954213), 4 SNPs in STAT4 (rs1467199, rs3821236, rs3024866, and rs7574865), 2 SNPs in BANK1 (rs10516487 and rs3733197), and 1 SNP in BLK (..
  18. Frucht D, Aringer M, Galon J, Danning C, Brown M, Fan S, et al. Stat4 is expressed in activated peripheral blood monocytes, dendritic cells, and macrophages at sites of Th1-mediated inflammation. J Immunol. 2000;164:4659-64 pubmed
    b>Stat4 is a key transcription factor involved in promoting cell-mediated immunity, whose expression in mature cells has been reported to be restricted to T and NK cells...
  19. Yang W, Ng P, Zhao M, Hirankarn N, Lau C, Mok C, et al. Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. Genes Immun. 2009;10:219-26 pubmed publisher
    ..from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3...
  20. Liang Y, Wu H, Li P, Xie X, Shen X, Yang X, et al. Signal transducer and activator of transcription 4 gene polymorphisms associated with rheumatoid arthritis in Northwestern Chinese Han population. Life Sci. 2011;89:171-5 pubmed publisher
    b>Signal transducer and activator of transcription 4 (STAT4) gene encode a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases...
  21. Barton A, Thomson W, Ke X, Eyre S, Hinks A, Bowes J, et al. Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility. Hum Mol Genet. 2008;17:2274-9 pubmed publisher
    ..We, therefore, investigated the evidence for association of the STAT4 and TRAF1/C5 loci with RA using imputed data from the Wellcome Trust Case Control Consortium (WTCCC)...
  22. Fung E, Smyth D, Howson J, Cooper J, Walker N, Stevens H, et al. Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus. Genes Immun. 2009;10:188-91 pubmed publisher
    ..cases and 9733 controls we found some evidence for an association with T1D in the regions containing genes: 2q32/STAT4, 17q21/STAT3, 5p15/ERAP1 (ARTS1), 6q23/TNFAIP3 and 12q13/KIF5A/PIP4K2C with allelic P-values ranging from 3...
  23. Morgan A, Robinson J, Conaghan P, Martin S, Hensor E, Morgan M, et al. Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort. Arthritis Res Ther. 2010;12:R57 pubmed publisher
    This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort...
  24. Hellquist A, Sandling J, Zucchelli M, Koskenmies S, Julkunen H, D Amato M, et al. Variation in STAT4 is associated with systemic lupus erythematosus in a Finnish family cohort. Ann Rheum Dis. 2010;69:883-6 pubmed publisher
    To investigate whether 10 single nucleotide polymorphisms (SNPs) and haplotypes in the STAT4 gene, previously associated with systemic lupus erythematosus (SLE) in a Swedish case-control cohort, are also associated with SLE risk in a ..
  25. Yi L, Wang J, Guo X, Gu Y, Tu W, Guo G, et al. STAT4 is a genetic risk factor for systemic sclerosis in a Chinese population. Int J Immunopathol Pharmacol. 2013;26:473-478 pubmed
    ..An association of single-nucleotide polymorphisms (SNPs) in the STAT4 gene with SSc has been reported in European Caucasians, North Americans and Japanese...
  26. Kisseleva T, Bhattacharya S, Braunstein J, Schindler C. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene. 2002;285:1-24 pubmed
    ..Similarly, the solution of the crystal structure of two STATs has and will continue to facilitate our understanding of how STATs function. This review will highlight these exciting developments in JAK/STAT signaling. ..
  27. Kawasaki A, Ito I, Hikami K, Ohashi J, Hayashi T, Goto D, et al. Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region. Arthritis Res Ther. 2008;10:R113 pubmed publisher
    Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32...
  28. Zervou M, Sidiropoulos P, Petraki E, Vazgiourakis V, Krasoudaki E, Raptopoulou A, et al. Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for rheumatoid arthritis in a genetically homogeneous population. Hum Immunol. 2008;69:567-71 pubmed publisher
    ..studies in different populations have recently revealed a significant association between a TRAF1/C5 and a STAT4 polymorphism and the development of RA...
  29. O Malley J, Eri R, Stritesky G, Mathur A, Chang H, HogenEsch H, et al. STAT4 isoforms differentially regulate Th1 cytokine production and the severity of inflammatory bowel disease. J Immunol. 2008;181:5062-70 pubmed
    b>STAT4, a critical regulator of inflammation in vivo, can be expressed as two alternative splice forms, a full-length STAT4alpha, and a STAT4beta isoform lacking a C-terminal transactivation domain...
  30. Li P, Cao C, Luan H, Li C, Hu C, Zhang S, et al. Association of genetic variations in the STAT4 and IRF7/KIAA1542 regions with systemic lupus erythematosus in a Northern Han Chinese population. Hum Immunol. 2011;72:249-55 pubmed publisher
    ..Genome-wide association studies have identified SLE susceptibility variations at the IRF7/KIAA1542 locus and with STAT4 gene in European populations...
  31. Zhernakova A, Stahl E, Trynka G, Raychaudhuri S, Festen E, Franke L, et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 2011;7:e1002004 pubmed publisher
    ..in either CD or RA are associated with the other autoimmune disease at combined P<5 × 10(-8) (SH2B3, 8q24, STAT4, and TRAF1-C5)...
  32. Daha N, Kurreeman F, Marques R, Stoeken Rijsbergen G, Verduijn W, Huizinga T, et al. Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis. Arthritis Rheum. 2009;60:1255-60 pubmed publisher
    ..Currently, 5 loci (HLA, PTPN22, TRAF1/C5, TNFAIP3, and STAT4) have been consistently reported, whereas others have been observed less systematically...
  33. Mells G, Floyd J, Morley K, Cordell H, Franklin C, Shin S, et al. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet. 2011;43:329-32 pubmed publisher
    ..New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1...
  34. Wang C, Sandling J, Hagberg N, Berggren O, Sigurdsson S, Karlberg O, et al. Genome-wide profiling of target genes for the systemic lupus erythematosus-associated transcription factors IRF5 and STAT4. Ann Rheum Dis. 2013;72:96-103 pubmed publisher
    The transcription factors interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) are encoded by two of the strongest susceptibility genes for systemic lupus erythematosus (SLE)...
  35. Kiyohara C, Washio M, Horiuchi T, Tada Y, Asami T, Ide S, et al. Cigarette smoking, STAT4 and TNFRSF1B polymorphisms, and systemic lupus erythematosus in a Japanese population. J Rheumatol. 2009;36:2195-203 pubmed publisher
    Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations...
  36. Martinez A, Varadé J, Marquez A, Cenit M, Espino L, Perdigones N, et al. Association of the STAT4 gene with increased susceptibility for some immune-mediated diseases. Arthritis Rheum. 2008;58:2598-602 pubmed publisher
    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...
  37. Yamamoto K, Quelle F, Thierfelder W, Kreider B, Gilbert D, Jenkins N, et al. Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation. Mol Cell Biol. 1994;14:4342-9 pubmed
    ..This approach allowed the identification and cloning of the Stat4 gene, which is 52% identical to STAT1...
  38. Sigurdsson S, Nordmark G, Garnier S, Grundberg E, Kwan T, Nilsson O, et al. A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5. Hum Mol Genet. 2008;17:2868-76 pubmed publisher
    ..Because signal transducer and activator of transcription 4 (STAT4) plays a key role in the type I IFN receptor signaling, we performed a candidate gene ..
  39. Plant D, Flynn E, Mbarek H, Dieude P, Cornelis F, Arlestig L, et al. Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers. Ann Rheum Dis. 2010;69:1548-53 pubmed publisher
    ..rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis...
  40. Diaz Gallo L, Palomino Morales R, Gómez Garcia M, Cardeña C, Rodrigo L, Nieto A, et al. STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: a replication study. Hum Immunol. 2010;71:515-9 pubmed publisher
    Recently, the signal transducer and activator of transcription 4 (STAT4) gene has been associated with multiple autoimmune diseases...
  41. Ben Hamad M, Cornelis F, Mbarek H, Chabchoub G, Marzouk S, Bahloul Z, et al. Signal transducer and activator of transcription and the risk of rheumatoid arthritis and thyroid autoimmune disorders. Clin Exp Rheumatol. 2011;29:269-74 pubmed
    The signal transducer and activator of transcription 4 (STAT4) gene localised on chromosome 2q32.2-q32...
  42. Tong G, Zhang X, Tong W, Liu Y. Association between polymorphism in STAT4 gene and risk of rheumatoid arthritis: a meta-analysis. Hum Immunol. 2013;74:586-92 pubmed publisher
    ..Single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 4 (STAT4) gene are suspected to have some relationship with the risk of RA...
  43. Chung S, Taylor K, Graham R, Nititham J, Lee A, Ortmann W, et al. Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production. PLoS Genet. 2011;7:e1001323 pubmed publisher
    ..SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE...
  44. Sugiura T, Kawaguchi Y, Goto K, Hayashi Y, Tsuburaya R, Furuya T, et al. Positive association between STAT4 polymorphisms and polymyositis/dermatomyositis in a Japanese population. Ann Rheum Dis. 2012;71:1646-50 pubmed publisher
    To investigate associations between signal transducer and activator of transcription 4 (STAT4), one of the most commonly acknowledged genes for the risk of multiple autoimmune diseases, with susceptibility to adult-onset polymyositis/..
  45. Kim S, Kim E, Moon C, Kim T, Kim W, Cheon J. Abnormal genetic and epigenetic changes in signal transducer and activator of transcription 4 in the pathogenesis of inflammatory bowel diseases. Dig Dis Sci. 2012;57:2600-7 pubmed
    Changes in the expression of signal transducer and activator of transcription 4 (STAT4) contribute to the development of a variety of autoimmune diseases including inflammatory bowel diseases (IBDs)...
  46. Palomino Morales R, Diaz Gallo L, Witte T, Anaya J, Martin J. Influence of STAT4 polymorphism in primary Sjögren's syndrome. J Rheumatol. 2010;37:1016-9 pubmed publisher
    To examine the influence of STAT4 rs7574865 gene polymorphism on patients with primary Sjögren's syndrome (SS)...
  47. Gourh P, Agarwal S, Divecha D, Assassi S, Paz G, Arora Singh R, et al. Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: evidence of possible gene-gene interaction and alterations in Th1/Th2 cytokines. Arthritis Rheum. 2009;60:3794-806 pubmed publisher
    ..This study was undertaken to investigate the hypothesis that single-nucleotide polymorphisms (SNPs) in TBX21 and STAT4, both of which are critical transcription factors that regulate the Th1/Th2 balance, are associated with SSc ..
  48. Zheng J, Yin J, Huang R, Petersen F, Yu X. Meta-analysis reveals an association of STAT4 polymorphisms with systemic autoimmune disorders and anti-dsDNA antibody. Hum Immunol. 2013;74:986-92 pubmed publisher
    b>Signal transducer and activator of transcription 4 (STAT4) has been recently identified as a susceptibility gene for multiple autoimmune diseases...
  49. Remoli M, Ragimbeau J, Giacomini E, Gafa V, Severa M, Lande R, et al. NF-{kappa}B is required for STAT-4 expression during dendritic cell maturation. J Leukoc Biol. 2007;81:355-63 pubmed
  50. Lee H, Remmers E, Le J, Kastner D, Bae S, Gregersen P. Association of STAT4 with rheumatoid arthritis in the Korean population. Mol Med. 2007;13:455-60 pubmed
    A recent study in the North American White population has documented the association of a common STAT4 haplotype (tagged by rs7574865) with risk for rheumatoid arthritis (RA) and systemic lupus erythematosus...
  51. Nakamura M, Nishida N, Kawashima M, Aiba Y, Tanaka A, Yasunami M, et al. Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population. Am J Hum Genet. 2012;91:721-8 pubmed publisher
    ..66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1...
  52. Palomino Morales R, Rojas Villarraga A, Gonzalez C, Ramirez G, Anaya J, Martin J. STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians. Genes Immun. 2008;9:379-82 pubmed publisher
    The aim of this study was to determine the influence of STAT4 (rs7574865) and TRAF1/C5 (rs10818488 and rs2900180) gene polymorphisms on the risk of developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a ..
  53. Kirino Y, Bertsias G, Ishigatsubo Y, Mizuki N, Tugal Tutkun I, Seyahi E, et al. Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1. Nat Genet. 2013;45:202-7 pubmed publisher
    ..We identified new associations at CCR1, STAT4 and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p...
  54. Jiang D, Sun J, Cao G, Liu Y, Lin D, Gao Y, et al. Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat Genet. 2013;45:72-5 pubmed publisher
    ..The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49...
  55. Dieude P, Wipff J, Guedj M, Ruiz B, Melchers I, Hachulla E, et al. BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4. Arthritis Rheum. 2009;60:3447-54 pubmed publisher
    ..Caucasian populations and to investigate the putative gene-gene interactions between BANK1 and IRF5 as well as STAT4. BANK1 single-nucleotide polymorphisms were genotyped in a total population of 2,432 individuals...
  56. Bacon C, Petricoin E, Ortaldo J, Rees R, Larner A, Johnston J, et al. Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes. Proc Natl Acad Sci U S A. 1995;92:7307-11 pubmed
    ..report we demonstrate that IL-12 induces tyrosine phosphorylation of a recently identified STAT family member, STAT4, and show that STAT4 expression is regulated by T-cell activation...
  57. Glas J, Seiderer J, Nagy M, Fries C, Beigel F, Weidinger M, et al. Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset. PLoS ONE. 2010;5:e10373 pubmed publisher
    Recent studies demonstrated an association of STAT4 variants with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), indicating that multiple autoimmune diseases share common susceptibility genes...
  58. Hu K, Yang P, Jiang Z, Hou S, Du L, Li F. STAT4 polymorphism in a Chinese Han population with Vogt-Koyanagi-Harada syndrome and Behçet's disease. Hum Immunol. 2010;71:723-6 pubmed publisher
    This study investigated the association of rs7574865 polymorphism in STAT4 with Vogt-Koyanagi-Harada (VKH) syndrome and Behçet's disease (BD) in a Chinese Han population...
  59. Radstake T, Gorlova O, Rueda B, Martin J, Alizadeh B, Palomino Morales R, et al. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet. 2010;42:426-9 pubmed publisher
    ..39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.
  60. Dieude P, Guedj M, Wipff J, Ruiz B, Hachulla E, Diot E, et al. STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis. Arthritis Rheum. 2009;60:2472-9 pubmed publisher
    ..The recent identification of an association between IRF5 and SSc further highlights a key role for IFN. STAT4, which encodes STAT-4, contributes to IFN signaling, and its genetic variants were found to be associated with ..
  61. Ji J, Lee W, Kong K, Woo J, Choi S, Lee Y, et al. Association of STAT4 polymorphism with rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep. 2010;37:141-7 pubmed publisher
    b>STAT4 is a transcription factor that has been implicated in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)...
  62. Hom G, Graham R, Modrek B, Taylor K, Ortmann W, Garnier S, et al. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med. 2008;358:900-9 pubmed publisher
    ..Alleles of HLA-DRB1, IRF5, and STAT4 are established susceptibility genes; there is strong evidence for the existence of additional risk loci...
  63. Rueda B, Broen J, Simeon C, Hesselstrand R, Diaz B, Suarez H, et al. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum Mol Genet. 2009;18:2071-7 pubmed publisher
    The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype...
  64. Clark A, Gerlach F, Tong H, Hoan N, Song L, Toan N, et al. A trivial role of STAT4 variant in chronic hepatitis B induced hepatocellular carcinoma. Infect Genet Evol. 2013;18:257-61 pubmed publisher
    Two polymorphisms in the STAT4 and HLA-DQ loci were more recently reported to associate with chronic hepatitis B (CHB) induced hepatocellular carcinoma (HCC)...
  65. Lee H, Park H, Yang S, Kim D, Park Y. STAT4 polymorphism is associated with early-onset type 1 diabetes, but not with late-onset type 1 diabetes. Ann N Y Acad Sci. 2008;1150:93-8 pubmed publisher
    ..genes affecting susceptibility to type 1 diabetes (T1D), we have investigated the association of polymorphisms in STAT4, an important signaling molecule of IL-12, gammaIFN, and IL-23, in a sample of 389 T1D patients and 152 ..
  66. Mirkazemi S, Akbarian M, Jamshidi A, Mansouri R, Ghoroghi S, Salimi Y, et al. Association of STAT4 rs7574865 with susceptibility to systemic lupus erythematosus in Iranian population. Inflammation. 2013;36:1548-52 pubmed publisher
    ..b>STAT4 has been newly identified as a susceptible gene in the development of SLE...
  67. Hou S, Yang Z, Du L, Jiang Z, Shu Q, Chen Y, et al. Identification of a susceptibility locus in STAT4 for Behçet's disease in Han Chinese in a genome-wide association study. Arthritis Rheum. 2012;64:4104-13 pubmed publisher
    ..Our GWAS and replication studies identified a susceptibility locus around STAT4 (single-nucleotide polymorphisms [SNPs] rs7574070, rs7572482, and rs897200; P = 3.36 × 10(-7) to 6...
  68. Liang Y, Wu H, Shen X, Li P, Yang X, Liang L, et al. Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis. Mol Biol Rep. 2012;39:8873-82 pubmed publisher
    The association between the signal transducer and activator of transcription 4 (STAT4) gene rs7574865 single nucleotide polymorphism and different autoimmune diseases remains controversial and ambiguous...
  69. Allanore Y, Saad M, Dieude P, Avouac J, Distler J, Amouyel P, et al. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis. PLoS Genet. 2011;7:e1002091 pubmed publisher
    ..The genetic signal of association with TNIP1 variants, together with tissular and cellular investigations, suggests that this pathway has a critical role in regulating autoimmunity and SSc pathogenesis. ..
  70. Han J, Zheng H, Cui Y, Sun L, Ye D, Hu Z, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet. 2009;41:1234-7 pubmed publisher
    ..77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12))...
  71. Hinks A, Eyre S, Ke X, Barton A, Martin P, Flynn E, et al. Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis. Ann Rheum Dis. 2010;69:1049-53 pubmed publisher
    ..Two JIA susceptibility loci were identified, one of which was a novel JIA association (STAT4) and the second confirmed previously published associations of the TRAF1/C5 locus with JIA...
  72. Chang H, Han L, Goswami R, Nguyen E, Pelloso D, Robertson M, et al. Impaired development of human Th1 cells in patients with deficient expression of STAT4. Blood. 2009;113:5887-90 pubmed publisher
    IL-12 activates STAT4, which is a critical regulator of inflammation and T helper type I (Th1) lineage development in murine systems. The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly...
  73. Graham R, Cotsapas C, Davies L, Hackett R, Lessard C, Leon J, et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:1059-61 pubmed publisher
    ..These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA. ..
  74. Abelson A, Delgado Vega A, Kozyrev S, Sanchez E, Velázquez Cruz R, Eriksson N, et al. STAT4 associates with systemic lupus erythematosus through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk. Ann Rheum Dis. 2009;68:1746-53 pubmed publisher
    To confirm and define the genetic association of STAT4 and systemic lupus erythematosus (SLE), investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5...
  75. Orozco G, Alizadeh B, Delgado Vega A, Gonzalez Gay M, Balsa A, Pascual Salcedo D, et al. Association of STAT4 with rheumatoid arthritis: a replication study in three European populations. Arthritis Rheum. 2008;58:1974-80 pubmed publisher
    This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a ..
  76. Yamamoto K, Kobayashi H, Arai A, Miura O, Hirosawa S, Miyasaka N. cDNA cloning, expression and chromosome mapping of the human STAT4 gene: both STAT4 and STAT1 genes are mapped to 2q32.2-->q32.3. Cytogenet Cell Genet. 1997;77:207-10 pubmed
    ..b>STAT4 is phosphorylated following interleukin (IL)-12 stimulation and is essential for IL-12 signal transduction...