Linn-Rasker S P, van der Helm-van Mil A H M, van Gaalen F A, Kloppenburg M, de Vries R R P, le Cessie S, Breedveld F C, Toes R E M, Huizinga T W J
Department of Rheumatology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, Netherlands.
Ann Rheum Dis. 2006 Mar;65(3):366-71. doi: 10.1136/ard.2005.041079. Epub 2005 Jul 13.
To study the gene-environment interaction of tobacco exposure and shared epitope on autoantibodies in patients with rheumatoid arthritis and undifferentiated arthritis.
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.
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.
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.
研究烟草暴露与共同表位在类风湿关节炎和未分化关节炎患者自身抗体中的基因 - 环境相互作用。
从关节炎新发病例（n = 1305）中，确定未符合任何分类标准的患者（未分化关节炎，n = 486）以及符合美国风湿病学会类风湿关节炎标准的患者（n = 407）。测定IgM类风湿因子（RF）、抗环瓜氨酸肽（CCP）抗体和HLA - DRB1等位基因。
在类风湿关节炎中，发现烟草暴露与共同表位在抗CCP抗体存在方面存在相互作用，因为同时有烟草暴露（TE）和共同表位（SE）的患者中抗CCP抗体的优势比高于仅有烟草暴露或共同表位的患者的优势比之和（优势比：TE + / SE - ，1.07；TE - / SE + ，2.49；TE + / SE + ，5.27 - 均相对于TE - / SE - ）。RF也有类似效应，但分层显示该相互作用主要与抗CCP抗体反应相关。在两周时处于未分化关节炎的患者或一年后持续处于未分化关节炎的患者中，未观察到烟草暴露与共同表位在自身抗体存在方面的相互作用。
烟草暴露仅在共同表位阳性的类风湿关节炎患者中增加抗CCP抗体的危险因素。吸烟与共同表位之间导致自身抗体的基因 - 环境相互作用是类风湿关节炎特有的，在未分化关节炎中未观察到。
