Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
BANK1 Is a Genetic Risk Factor for Diffuse Cutaneous Systemic Sclerosis Having Additive Effects with IRF5 and STAT4
Dieude1, Philippe, Guedj2, Mickael, Wippf3, Julien, Melchers4, Inga, Boileau5, Catherine, Allanore3, Yannick, GFRS and DNSS co-workers,
Bichat Claude-bernard, Universitary Hospital, APHP, Paris, France
Université d'Evry Val d'Essonne, Evry, France
Paris Descartes Univ, Paris, France
University Medical Center, Freiburg, Germany
Hôpital Ambroise Paré, AP-HP, Boulogne, France
Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) share common genetic risk factors including IRF5 and STAT4 variants. Polymorphisms of the B-cell scaffold protein with ankyrin repeats gene, BANK1, were recently identified as SLE risk factors.
To determine whether the functional BANK1 rs3733197 and rs10516487 variants are associated with SSc in European Caucasians populations. To investigate the putative gene-gene interaction between BANK1 and IRF5 and STAT4.
BANK1 SNPs were genotyped in 2407 individuals comprising a French set (874 SSc patients and 955 controls, previously genotyped for both IRF5 rs2004640 and STAT4 rs7574865) and a German set (421 SSc patients and 182 controls).
The BANK1 variants were found to be associated with the diffuse cutaneous SSc (dcSSc) in both samples providing an OR of 0.77 for the rs10516487 T rare allele in the combined populations compared to controls (95%CI [0.640.93]) and an OR of 0.73 (95%CI [0.610.87]) for the rs3733197 A rare allele. BANK1 haplotype analysis found the A-T haplotype to be protective in dcSSc (P=0.0003, OR 0.70 [95% CI 0.570.86]) and the G-C haplotype to be a risk factor (P= 0.008, OR 1.25 [95% CI 1.061.47]). Significant differences were also observed when the limited cutaneous subset of SSc was compared to dcSSc both for rare alleles and haplotypes. The BANK1, IRF5 and STAT4 risk alleles risk alleles displayed a multiplicatively increased 1.43-fold risk of dcSSc (Figure).
Figure. Joint effects of risk alleles of BANK1 (rs10516487 & rs3733197) STAT4 (rs7574865) and IRF5 (rs2004640) on SSc and dcSSc susceptibility
Our results establish BANK1 as a new SSc genetic susceptibility factor and BANK1, IRF5 and STAT4 act with additive effects.
To cite this abstract, please use the following information:
Dieude, Philippe, Guedj, Mickael, Wippf, Julien, Melchers, Inga, Boileau, Catherine, Allanore, Yannick, et al; BANK1 Is a Genetic Risk Factor for Diffuse Cutaneous Systemic Sclerosis Having Additive Effects with IRF5 and STAT4 [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1802