Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Association and Linkage Proof for IRF5 as a Rheumatoid Arthritis Susceptibility Gene

Dawidowicz1,  Karen, Allanore2,  Yannick, Pierlot3,  Céline, Teixeira3,  Vitor-Hugo, Petit-Teixeira3,  Elisabeth, Cornelis3,  Francois, Dieude1,  P.

Bichat Claude-bernard, Universitary Hospital, APHP, Paris, France
Paris Descartes Univ, Paris, France
Evry University, Evry-Genopole, France


Type 1 IFNs play a key role in autoimmunity when tolerance is lost and autoreactivity appears. Increased expression of type 1 IFN genes, also referred as an IFN signature, has been detected in various autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis (RA), Sjögren's syndrome and in a subgroup of systemic sclerosis patients. Interferon regulatory factors, such as IRF5, coordinate type I IFNs expression. To date, multiple IRF5 variants were suggested as susceptibility genetic factors of various autoimmune diseases, including RA.


As the linkage proof remains important to fully establish IRF5 as genetic RA susceptibility factor, we aimed at providing it, tacking advantage of the largest reported European family resource dedicated to RA linkage studies.


Overall, 1014 European Caucasian individuals from 338 RA trio families were genotyped for IRF5 rs3757385, rs2004640 and rs10954213 single nucleotide polymorphisms (SNPs).


Single marker analysis provided linkage evidence for each IRF5 SNP investigated. IRF5 linked to RA with two significant haplotypes out of 8. The IRF5 C-T-A susceptible haplotype "S" (T= 62.2%, P= 2.9×10-4) and the A-G-G protective haplotype "P" (T= 38.7%, P= 1.86×10-3). Linkage was significantly stronger in non-erosive disease for both IRF5 S and P haplotypes: T= 82.2%, P= 1.34×10-5 and T= 19.4%, P= 2.46×10-4, respectively. No other significant independent clinical, including ACPA status, nor genetic factor influencing linkage was detected. IRF5 homozygous haplotypic genotypes SS and PP were strongly associated with RA: P= 0.0026, OR1.88, 95%CI [1.24–2.84], P= 0.006, OR 0.71 95%CI [0.55–0.91], respectively. leading us to purpose a practical approach according to the IRF5 SS, PP and XX haplotypic genotype individual status (X being non-S and non-P haplotypes).


This study provides the final piece of the "association and linkage proof" for IRF5 as a RA susceptibility gene and led to the identification of a potential factor which could influence the rheumatoid erosive phenotype. Further studies in inception cohorts are required to clarify the role played by IRF5 in the rheumatoid arthritis erosive phenotype.

To cite this abstract, please use the following information:
Dawidowicz, Karen, Allanore, Yannick, Pierlot, Céline, Teixeira, Vitor-Hugo, Petit-Teixeira, Elisabeth, Cornelis, Francois, et al; Association and Linkage Proof for IRF5 as a Rheumatoid Arthritis Susceptibility Gene [abstract]. Arthritis Rheum 2009;60 Suppl 10 :576
DOI: 10.1002/art.25656

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