Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis
Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis
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DOI：
10.1002/art.22704
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发表时间：
2007-07-01
影响因子：
--
通讯作者：
Ronnblom, Lars
中科院分区：
文献类型：
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作者：
Sigurdsson, Snaevar;Padyukov, Leonid;Ronnblom, Lars
目标。目的：探讨干扰素调节因子5 （IRF-5）和Tyk-2基因的遗传变异是否与类风湿关节炎（RA）相关。在瑞典的1530例RA患者和881例对照中分析了JRF5的5个单核苷酸多态性（snp）和Tyk2的3个snp。在荷兰的387例RA患者和181例对照组中进行了一项重复研究。检测所有患者血清中抗环瓜氨酸肽（anti-CCP）自身抗体的存在。位于IRF5 5'区的5个SNPs中有4个与RA相关，而与Tyk2 SNPs没有关联。其中3个IRF5 snp的小等位基因处于连锁不平衡状态，形成了一个相对常见的单倍型，频率接近0.33，似乎对RA具有保护作用。尽管这些疾病关联在整个患者组中都存在，但主要出现在抗ccp阴性的RA患者中。在荷兰队列中也观察到IRF5 snp与抗ccp阴性RA的相关性。鉴于抗ccp阴性RA与抗ccp阳性RA在遗传和环境风险因素方面存在差异，我们的研究结果表明，IRF5的遗传变异导致了抗ccp阴性RA独特的病因和发病机制。
Objective. To determine whether genetic variants of the interferon regulatory factor 5 (IRF-5) and Tyk-2 genes are associated with rheumatoid arthritis (RA).Methods. Five single-nucleotide polymorphisms (SNPs) in JRF5 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 autoantibodlies against cyclic citrullinated peptides (anti-CCP).Results. 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 similar to 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.Conclusion. 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.