Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Common Genetic Background for Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Orozco,  Gisela, Eyre,  Steve, Hinks,  Anne, Thomson,  Wendy, Worthington,  Jane, Barton,  Anne

Background:

Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases.

The aim of this study was to investigate single nucleotide polymorphisms (SNP) that have been reported to be associated with SLE in a UK cohort of RA cases and controls.

Methods:

3,962 RA patients and 9,275 controls were included in the study. Of the SLE loci identified to date (1), eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotyping was undertaken using a Sequenom platform with iPlex chemistry. Genotype frequencies were compared between RA cases and controls using the trend test implemented in PLINK software. P-values <0.0045 were regarded as significant after correcting for multiple testing.

Summary of Results:

The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA (rs2736340, P= 3.0 × 10-4, OR 1.11 95% CI 1.05–1.17; rs5754217, P= 2.4 × 10-3, OR 1.11 95% CI 1.04–1.19). Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (P=0.02 and P=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, we found a significant global enrichment in carriage of SLE alleles in RA patients compared to controls (P= 9.1 × 10-7). Meta-analysis of this and previous studies confirm the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (P<5×10-8). Together, we estimate that, after excluding HLA-DRB1 alleles, the overlapping loci identified so far explain ~5.8% of the genetic susceptibility to RA as a whole.

Conclusions:

The findings confirm the association of the BLK and UBE2L3 loci with RA thus adding to the list of loci showing overlap between RA and SLE, which currently include HLA-DRB1, PTPN22, STAT4, TNFAIP3, FCGR2A, PRDM1, IRF5 and PXK.

References:

(1)GatevaSandlingHomTaylorChungSun, VJKGKESAX et al.A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009; 41(11):1228–33.

To cite this abstract, please use the following information:
Orozco, Gisela, Eyre, Steve, Hinks, Anne, Thomson, Wendy, Worthington, Jane, Barton, Anne; Common Genetic Background for Rheumatoid Arthritis and Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1075
DOI: 10.1002/art.28842

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