Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis

Wiley - Tập 56 Số 7 - Trang 2202-2210 - 2007
Snævar Sigurðsson1, Leonid Padyukov2, Fina Kurreeman3, Ulrika Liljedahl1, Ann-Christin Wiman1, Lars Alfredsson4, René E. M. Toes3, Johan Rönnelid1, Lars Klareskog2, T. Huizinga3, Gunnar V. Alm5, Chris Wallace1, Lars Rönnblom1
1Uppsala University, Uppsala, Sweden
2Karolinska University Hospital, Solna, and Karolinska Institutet, Stockholm, Sweden
3Leiden University Medical Center, Leiden, The Netherlands.
4Karolinska Institutet, Stockholm, Sweden
5Swedish University of Agricultural Sciences, Uppsala, Sweden

Tóm tắt

AbstractObjectiveTo determine whether genetic variants of the interferon regulatory factor 5 (IRF‐5) and Tyk‐2 genes are associated with rheumatoid arthritis (RA).MethodsFive 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).ResultsFour 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 ∼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.ConclusionGiven 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.

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Wiley

Tập 56 Số 7

2202-2210

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