Sigurdsson Snaevar, Padyukov Leonid, Kurreeman Fina A S, Liljedahl Ulrika, Wiman Ann-Christin, Alfredsson Lars, Toes René, Rönnelid Johan, Klareskog Lars, Huizinga Tom W J, Alm Gunnar, Syvänen Ann-Christine, Rönnblom Lars
Uppsala University, Uppsala, Sweden.
Arthritis Rheum. 2007 Jul;56(7):2202-10. doi: 10.1002/art.22704.
To determine whether genetic variants of the interferon regulatory factor 5 (IRF-5) and Tyk-2 genes are associated with rheumatoid arthritis (RA).
Five single-nucleotide polymorphisms (SNPs) in IRF5 and 3 SNPs in Tyk2 were analyzed in a Swedish cohort of 1,530 patients with RA and 881 controls. A replication study was performed in a Dutch cohort of 387 patients with RA and 181 controls. All patient sera were tested for the presence of autoantibodies against cyclic citrullinated peptides (anti-CCP).
Four of the 5 SNPs located in the 5' region of IRF5 were associated with RA, while no association was observed with the Tyk2 SNPs. The minor alleles of 3 of the IRF5 SNPs, which were in linkage disequilibrium and formed a relatively common haplotype with a frequency of approximately 0.33, appeared to confer protection against RA. Although these disease associations were seen in the entire patient group, they were mainly found in RA patients who were negative for anti-CCP. A suggestive association of IRF5 SNPs with anti-CCP-negative RA was also observed in the Dutch cohort.
Given the fact that anti-CCP-negative RA differs from anti-CCP-positive RA with respect to genetic and environmental risk factor profiles, our results indicate that genetic variants of IRF5 contribute to a unique disease etiology and pathogenesis in anti-CCP-negative RA.
确定干扰素调节因子5（IRF-5）和酪氨酸激酶2（Tyk-2）基因的遗传变异是否与类风湿关节炎（RA）相关。
在一个由1530例RA患者和881例对照组成的瑞典队列中，分析了IRF5基因的5个单核苷酸多态性（SNP）和Tyk2基因的3个SNP。在一个由387例RA患者和181例对照组成的荷兰队列中进行了重复研究。检测所有患者血清中抗环瓜氨酸肽自身抗体（抗CCP）的存在情况。
位于IRF5基因5'区域的5个SNP中有4个与RA相关，而未观察到Tyk2基因的SNP与RA有关联。IRF5基因的3个SNP的次要等位基因处于连锁不平衡状态，形成了一个频率约为0.33的相对常见单倍型，似乎对RA有保护作用。尽管在整个患者组中观察到了这些疾病关联，但主要见于抗CCP阴性的RA患者。在荷兰队列中也观察到IRF5基因SNP与抗CCP阴性RA之间存在提示性关联。
鉴于抗CCP阴性RA在遗传和环境危险因素方面与抗CCP阳性RA不同，我们的结果表明IRF5基因变异在抗CCP阴性RA中促成了独特的疾病病因和发病机制。
