RT Journal Article
SR Electronic
T1 Phenotype-Haplotype Correlation of IRF5 in Systemic Sclerosis: Role of 2 Haplotypes in Disease Severity
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.091163
DO 10.3899/jrheum.091163
A1 Philippe Dieude
A1 Karen Dawidowicz
A1 Mickaël Guedj
A1 Yona Legrain
A1 Julien Wipff
A1 Eric Hachulla
A1 Elisabeth Diot
A1 Jean Sibilia
A1 Luc Mouthon
A1 Jean Cabane
A1 Zahir Amoura
A1 Jean-Luc Crakowski
A1 Patrick Carpentier
A1 Jerome Avouac
A1 Olivier Meyer
A1 Andre Kahan
A1 Catherine Boileau
A1 Yannick Allanore
YR 2010
UL http://www.jrheum.org/content/early/2010/03/12/jrheum.091163.abstract
AB Objective Identification of an association between IRF5 rs2004640 and systemic sclerosis (SSc) has highlighted a key role for type 1 interferon (IFN). Additional functional IRF5 variants have been identified as autoimmune susceptibility factors. Our aim was to investigate whether IRF5 haplotypes confer susceptibility to SSc, and to perform genotype haplotype-phenotype correlation analyses. Methods We genotyped IRF5 rs377385, rs2004640, and rs10954213 in 1623 individuals of French European Caucasian origin. SSc patient subphenotypes were analyzed according to cutaneous subsets and for SSc-related pulmonary fibrosis. Results Case-control studies of single markers revealed an association between IRF5 rs3757385, rs2004640, and rs10954213 variants and SSc. We identified an IRF5 risk haplotype “R” (padj = 0.024, OR 1.23, 95% CI 1.07–1.40) and a mirrored protective haplotype “P” (padj = 8.8 × 10–3, OR 0.78, 95% CI 0.68–0.90) for SSc susceptibility. Genotype-phenotype correlation analyses failed to detect any association with a single marker. By contrast, phenotype-haplotype correlation analysis was able to detect intra-cohort association and to discriminate SSc patients with from those without the following clinical traits: “R” and/or “P” haplotypes identified diffuse cutaneous SSc (p = 0.0081) and fibrosing alveolitis (p = 0.018). Conclusion IRF5 haplotypes are more informative than single markers, suggesting that they could be helpful for risk stratification of SSc patients. Our study provides further evidence of a key role of IRF5 in SSc severity.