Barton Anne, Eyre Steve, Ke Xiayi, Hinks Anne, Bowes John, Flynn Edward, Martin Paul, Wilson Anthony G, Morgan Ann W, Emery Paul, Steer Sophia, Hocking Lynne J, Reid David M, Harrison Pille, Wordsworth Paul, Thomson Wendy, Worthington Jane
University of Manchester, Manchester, UK.
Hum Mol Genet. 2009 Jul 1;18(13):2518-22. doi: 10.1093/hmg/ddp177. Epub 2009 Apr 9.
The concept of susceptibility genes common to different autoimmune diseases is now firmly established with previous studies demonstrating overlap of loci conferring susceptibility to type 1 diabetes (T1D) with both Coeliac disease and multiple sclerosis. Rheumatoid arthritis (RA) is an archetypal autoimmune disease and we, therefore, targeted putative T1D susceptibility loci for genotyping in UK RA cases and unrelated controls. A novel RA susceptibility locus at AFF3 was identified with convincing evidence for association in a combined sample cohort of 6819 RA cases and 12 650 controls [OR 1.12 95% confidence intervals (CI) 1.07-1.17, P = 2.8 x 10(-7)]. Association of two previously described loci (CTLA-4 and 4q27) with RA was also replicated (OR 0.87, 95% CI 0.82-0.94, P = 1.1 x 10(-4) and OR 0.86, 95% CI 0.79-0.94, P = 5.4 x 10(-4), respectively). These findings take the number of established RA susceptibility loci to 13, only one of which has not been associated with other autoimmune diseases.
不同自身免疫性疾病共有的易感基因概念现已得到确凿证实，先前的研究表明，1型糖尿病（T1D）的易感位点与乳糜泻和多发性硬化症存在重叠。类风湿性关节炎（RA）是一种典型的自身免疫性疾病，因此，我们针对英国RA患者和无关对照中的假定T1D易感位点进行基因分型。在AFF3发现了一个新的RA易感位点，在6819例RA患者和12650例对照的联合样本队列中有令人信服的关联证据[比值比（OR）1.12，95%置信区间（CI）1.07 - 1.17，P = 2.8×10⁻⁷]。两个先前描述的位点（CTLA - 4和4q27）与RA的关联也得到了重复验证（分别为OR 0.87，95% CI 0.82 - 0.94，P = 1.1×10⁻⁴和OR 0.86，95% CI 0.79 - 0.94，P = 5.4×10⁻⁴）。这些发现使已确定的RA易感位点数量增加到13个，其中只有一个与其他自身免疫性疾病无关。
