OP0362 Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis. (12th June 2018)

• Record Type: Journal Article
• Authors: Leonard, D.; Svenungsson, E.; Dahlqvist, J.; Alexsson, A.; Ärlestig, L.; Taylor, K.E.; Sandling, J.K.; Bengtsson, C.; Frodlund, M.; Jönsen, A.; Eketjäll, S.; Jensen-Urstad, K.; Gunnarsson, I.; Sjöwall, C.; Bengtsson, A.A.; Eloranta, M.-L.; Syvänen, A.-C.; Rantapää-Dahlqvist, S.; Criswell, L.A.; Rönnblom, L.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 226
• Page End: 226
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.5381
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Patients with Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) have increased risk of cardiovascular disease (CVD). Objectives: We investigated whether single nucleotide polymorphisms (SNPs) at autoimmunity risk loci were associated with CVD in SLE and RA. Methods: SLE patients (n=1045) were genotyped using the 200K Immunochip SNP array (Illumina). The allele frequency was compared between patients with and without different manifestations of CVD. Results were replicated in a second SLE cohort (n=1043) and in an RA cohort (n=824). We analysed publically available genetic data from the general population, performed electrophoretic mobility shift assays and measured cytokine levels and occurrence of anti-phospholipid antibodies (aPLs). Results: We identified two new putative risk loci associated with increased risk for CVD in two SLE populations, which remained after adjustment for traditional CVD risk factors. An IL19 risk allele was associated with stroke/myocardial infarction in SLE (OR 2.3 (1.5–3.4), p=8.5×10–5) and RA (OR 2.8 (1.4–5.6), p=3.8×10–3), meta-analysis (OR 2.5 (2.0–2.9), p=3.5×10–7), but not in population controls. The IL19 risk allele affected protein binding and SLE patients with the risk allele had increased levels of plasma-IL10 (p=0.004) and aPL (p=0.01). An SRP54-AS1 risk allele was associated with stroke/transient ischaemic attack in SLE (OR 1.7 (1.3–2.2), p=2.5×10–5) but not in RA. The SRP54-AS1 risk allele is an expression quantitative trait locus for four genes. Conclusions: The IL19 risk allele was associated with stroke/myocardial infarction in SLE and RA, but not in the general population, indicating that shared immune pathways may be involved in the CVD pathogenesis in inflammatory rheumatic diseases. Disclosure of Interest: None declared