OBJECTIVES: To study the gene-environment interaction of tobacco exposure and shared epitope on autoantibodies in patients with rheumatoid arthritis and undifferentiated arthritis. METHODS: From incident cases of arthritis (n = 1305), patients who did not fulfil any classification criteria (undifferentiated arthritis (n = 486)) and those who fulfilled the American College of Rheumatology criteria for rheumatoid arthritis (n = 407) were identified. IgM rheumatoid factor (RF), anti-cyclic-citrullinated peptide (CCP) antibodies, and HLA-DRB1 alleles were determined. RESULTS: In rheumatoid arthritis, an interaction was found between tobacco exposure and shared epitope for the presence of anti-CCP antibodies, as the odds ratio for anti-CCP antibodies in patients having both tobacco exposure (TE) and shared epitope (SE) was higher than the summed odds ratios of patients having only tobacco exposure or shared epitope (odds ratios: TE+/SE-, 1.07; TE-/SE+, 2.49; and TE+/SE+, 5.27-all relative to TE-/SE-). A similar effect was found for RF, but stratification showed that the interaction primarily associated with the anti-CCP antibody response. In patients with undifferentiated arthritis at two weeks, or with persistent undifferentiated arthritis after one year, no interaction between tobacco exposure and shared epitope was observed for the presence of autoantibodies. CONCLUSIONS: Tobacco exposure increases the risk factor for anti-CCP antibodies only in shared epitope positive patients with rheumatoid arthritis. The gene-environment interaction between smoking and shared epitope leading to autoantibodies is specific for rheumatoid arthritis and is not observed in undifferentiated arthritis.
OBJECTIVES: To study the gene-environment interaction of tobacco exposure and shared epitope on autoantibodies in patients with rheumatoid arthritis and undifferentiated arthritis. METHODS: From incident cases of arthritis (n = 1305), patients who did not fulfil any classification criteria (undifferentiated arthritis (n = 486)) and those who fulfilled the American College of Rheumatology criteria for rheumatoid arthritis (n = 407) were identified. IgM rheumatoid factor (RF), anti-cyclic-citrullinated peptide (CCP) antibodies, and HLA-DRB1 alleles were determined. RESULTS: In rheumatoid arthritis, an interaction was found between tobacco exposure and shared epitope for the presence of anti-CCP antibodies, as the odds ratio for anti-CCP antibodies in patients having both tobacco exposure (TE) and shared epitope (SE) was higher than the summed odds ratios of patients having only tobacco exposure or shared epitope (odds ratios: TE+/SE-, 1.07; TE-/SE+, 2.49; and TE+/SE+, 5.27-all relative to TE-/SE-). A similar effect was found for RF, but stratification showed that the interaction primarily associated with the anti-CCP antibody response. In patients with undifferentiated arthritis at two weeks, or with persistent undifferentiated arthritis after one year, no interaction between tobacco exposure and shared epitope was observed for the presence of autoantibodies. CONCLUSIONS:Tobacco exposure increases the risk factor for anti-CCP antibodies only in shared epitope positive patients with rheumatoid arthritis. The gene-environment interaction between smoking and shared epitope leading to autoantibodies is specific for rheumatoid arthritis and is not observed in undifferentiated arthritis.
Authors: Derek L Mattey; Peter T Dawes; June Fisher; Ann Brownfield; Wendy Thomson; Ali H Hajeer; William E R Ollier Journal: J Rheumatol Date: 2002-11 Impact factor: 4.666
Authors: Tom W J Huizinga; Christopher I Amos; Annette H M van der Helm-van Mil; Wei Chen; Floris A van Gaalen; Damini Jawaheer; Geziena M T Schreuder; Mark Wener; Ferdinand C Breedveld; Naila Ahmad; Raymond F Lum; Rene R P de Vries; Peter K Gregersen; Rene E M Toes; Lindsey A Criswell Journal: Arthritis Rheum Date: 2005-11
Authors: L R Lard; M Boers; A Verhoeven; K Vos; H Visser; J M W Hazes; A H Zwinderman; G M T Schreuder; F C Breedveld; R R P De Vries; S van der Linden; E Zanelli; T W J Huizinga Journal: Arthritis Rheum Date: 2002-04
Authors: Jing Shi; Rachel Knevel; Parawee Suwannalai; Michael P van der Linden; George M C Janssen; Peter A van Veelen; Nivine E W Levarht; Annette H M van der Helm-van Mil; Anthony Cerami; Tom W J Huizinga; Rene E M Toes; Leendert A Trouw Journal: Proc Natl Acad Sci U S A Date: 2011-10-10 Impact factor: 11.205
Authors: Munitta Muthana; Sarah Hawtree; Adam Wilshaw; Eimear Linehan; Hannah Roberts; Sachin Khetan; Gbadebo Adeleke; Fiona Wright; Mohammed Akil; Ursula Fearon; Douglas Veale; Barbara Ciani; Anthony G Wilson Journal: Proc Natl Acad Sci U S A Date: 2015-08-27 Impact factor: 11.205