BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. METHODS: We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. 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 America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. RESULTS: A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. CONCLUSIONS: A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. Copyright 2007 Massachusetts Medical Society.
BACKGROUND:Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. METHODS: We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. 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 America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. RESULTS: A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. CONCLUSIONS: A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. Copyright 2007 Massachusetts Medical Society.
Authors: Paul I W de Bakker; Roman Yelensky; Itsik Pe'er; Stacey B Gabriel; Mark J Daly; David Altshuler Journal: Nat Genet Date: 2005-10-23 Impact factor: 38.330
Authors: Robert M Plenge; Leonid Padyukov; Elaine F Remmers; Shaun Purcell; Annette T Lee; Elizabeth W Karlson; Frederick Wolfe; Daniel L Kastner; Lars Alfredsson; David Altshuler; Peter K Gregersen; Lars Klareskog; John D Rioux Journal: Am J Hum Genet Date: 2005-11-01 Impact factor: 11.025
Authors: E M Tan; A S Cohen; J F Fries; A T Masi; D J McShane; N F Rothfield; J G Schaller; N Talal; R J Winchester Journal: Arthritis Rheum Date: 1982-11
Authors: K L Moser; B R Neas; J E Salmon; H Yu; C Gray-McGuire; N Asundi; G R Bruner; J Fox; J Kelly; S Henshall; D Bacino; M Dietz; R Hogue; G Koelsch; L Nightingale; T Shaver; N I Abdou; D A Albert; C Carson; M Petri; E L Treadwell; J A James; J B Harley Journal: Proc Natl Acad Sci U S A Date: 1998-12-08 Impact factor: 11.205
Authors: Ann B Begovich; Victoria E H Carlton; Lee A Honigberg; Steven J Schrodi; Anand P Chokkalingam; Heather C Alexander; Kristin G Ardlie; Qiqing Huang; Ashley M Smith; Jill M Spoerke; Marion T Conn; Monica Chang; Sheng-Yung P Chang; Randall K Saiki; Joseph J Catanese; Diane U Leong; Veronica E Garcia; Linda B McAllister; Douglas A Jeffery; Annette T Lee; Franak Batliwalla; Elaine Remmers; Lindsey A Criswell; Michael F Seldin; Daniel L Kastner; Christopher I Amos; John J Sninsky; Peter K Gregersen Journal: Am J Hum Genet Date: 2004-06-18 Impact factor: 11.025
Authors: Eli A Stahl; Soumya Raychaudhuri; Elaine F Remmers; Gang Xie; Stephen Eyre; Brian P Thomson; Yonghong Li; Fina A S Kurreeman; Alexandra Zhernakova; Anne Hinks; Candace Guiducci; Robert Chen; Lars Alfredsson; Christopher I Amos; Kristin G Ardlie; Anne Barton; John Bowes; Elisabeth Brouwer; Noel P Burtt; Joseph J Catanese; Jonathan Coblyn; Marieke J H Coenen; Karen H Costenbader; Lindsey A Criswell; J Bart A Crusius; Jing Cui; Paul I W de Bakker; Philip L De Jager; Bo Ding; Paul Emery; Edward Flynn; Pille Harrison; Lynne J Hocking; Tom W J Huizinga; Daniel L Kastner; Xiayi Ke; Annette T Lee; Xiangdong Liu; Paul Martin; Ann W Morgan; Leonid Padyukov; Marcel D Posthumus; Timothy R D J Radstake; David M Reid; Mark Seielstad; Michael F Seldin; Nancy A Shadick; Sophia Steer; Paul P Tak; Wendy Thomson; Annette H M van der Helm-van Mil; Irene E van der Horst-Bruinsma; C Ellen van der Schoot; Piet L C M van Riel; Michael E Weinblatt; Anthony G Wilson; Gert Jan Wolbink; B Paul Wordsworth; Cisca Wijmenga; Elizabeth W Karlson; Rene E M Toes; Niek de Vries; Ann B Begovich; Jane Worthington; Katherine A Siminovitch; Peter K Gregersen; Lars Klareskog; Robert M Plenge Journal: Nat Genet Date: 2010-05-09 Impact factor: 38.330
Authors: Wenfeng Tan; Hui Wu; Jian Zhao; Lezlie A Derber; David M Lee; Nancy A Shadick; Doyt L Conn; Edwin A Smith; Vivian H Gersuk; Gerald T Nepom; Larry W Moreland; Daniel E Furst; Susan D Thompson; Beth L Jonas; V Michael Holers; David N Glass; Pojen P Chen; S Louis Bridges; Michael E Weinblatt; Harold E Paulus; Betty P Tsao Journal: Arthritis Rheum Date: 2010-10