Kazkaz Leyla, Marotte Hubert, Hamwi Mayassa, Angélique Cazalis Marie, Roy Pascal, Mougin Bruno, Miossec Pierre
Clinical Immunology Unit, Departments of Immunology and Rheumatology, Hôpital Edouard Hérriot, 69437 Lyon Cedex 03, France.
Ann Rheum Dis. 2007 Feb;66(2):195-201. doi: 10.1136/ard.2004.033829. Epub 2006 Oct 26.
To investigate whether ethnic differences exist in the effect of the shared epitope and selected cytokine gene polymorphisms on the susceptibility and severity of rheumatoid arthritis in Syria (Damascus) and France (Rhône-Alpes area).
156 patients with rheumatoid arthritis and 120 healthy controls from Syria were compared with 512 patients with rheumatoid arthritis and 471 healthy controls from France. Shared epitope status, cytokine gene polymorphisms interleukin (IL)-1B +3954, IL-1RN +2018 and tumour necrosis factor alpha promoter (-238 and -308) were analysed by enzyme-linked oligosorbent assay. Joint destruction was defined by a right wrist Larsen score > or =2. Odds ratios (ORs) were calculated.
In both countries, a dose effect was observed between the shared epitope copy number and rheumatoid arthritis (Syria: OR 1 v 0 copies = 1.6, p = NS; OR 2 v 0 = 15.3, p<0.01; and France: OR 1 v 0 = 2.3, p<0.001; OR 2 v 0 = 7.2, p<0.001). A dose effect was also observed between the shared epitope copy number and joint destruction in Syria (OR 1 v 0 = 2.2, p = NS; OR 2 v 0 = 9.9, p<0.01) and France (OR 1 v 0 = 1.8, p<0.01; OR 2 v 0 = 4.8, p = 0.001). The dose effect of the shared epitope was greater in Syria than in France. Only the -238 tumour necrosis factor alpha polymorphism was associated with joint destruction in the Syrian population (p<0.05). However, after adjustment for age, sex, disease duration and rheumatoid factor for severity, this association disappeared.
The frequency of the shared epitope was increased in the French population with rheumatoid arthritis and in controls, but the association between the shared epitope and joint destruction was more pronounced in the Syrian population, with an OR of almost 10 for the homozygotes.
研究共同表位和选定的细胞因子基因多态性对叙利亚（大马士革）和法国（罗讷-阿尔卑斯地区）类风湿关节炎易感性和严重程度的影响是否存在种族差异。
将来自叙利亚的156例类风湿关节炎患者和120例健康对照与来自法国的512例类风湿关节炎患者和471例健康对照进行比较。通过酶联寡吸附测定法分析共同表位状态、细胞因子基因多态性白细胞介素（IL）-1B +3954、IL-1RN +2018和肿瘤坏死因子α启动子（-238和-308）。关节破坏定义为右手腕Larsen评分≥2。计算比值比（OR）。
在两个国家，均观察到共同表位拷贝数与类风湿关节炎之间存在剂量效应（叙利亚：OR 1对0拷贝 = 1.6，p = 无显著性差异；OR 2对0 = 15.3，p<0.01；法国：OR 1对0 = 2.3，p<0.001；OR 2对0 = 7.2，p<0.001）。在叙利亚（OR 1对0 = 2.2，p = 无显著性差异；OR 2对0 = 9.9，p<0.01）和法国（OR 1对0 = 1.8，p<0.01；OR 2对0 = 4.8，p = 0.001），共同表位拷贝数与关节破坏之间也观察到剂量效应。叙利亚共同表位的剂量效应大于法国。仅-238肿瘤坏死因子α多态性与叙利亚人群的关节破坏相关（p<0.05）。然而，在对年龄、性别、病程和类风湿因子进行严重程度校正后，这种关联消失。
法国类风湿关节炎患者和对照人群中共同表位的频率增加，但共同表位与关节破坏之间的关联在叙利亚人群中更为明显，纯合子的OR接近10。
