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Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis.
Uppsala University, Uppsala, Sweden.
Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Uppsala University, Uppsala, Sweden.
Rheumatology, Uppsala University, Uppsala, Sweden.
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2018 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 7, p. 1063-1069Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). We investigated whether single nucleotide polymorphisms (SNPs) at autoimmunity risk loci were associated with CVD in SLE and RA.

METHODS: Patients with SLE (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 publicly available genetic data from general population, performed electrophoretic mobility shift assays and measured cytokine levels and occurrence of antiphospholipid 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, rs17581834(T) was associated with stroke/myocardial infarction (MI) in SLE (OR 2.3 (1.5 to 3.4), P=8.5×10-5) and RA (OR 2.8 (1.4 to 5.6), P=3.8×10-3), meta-analysis (OR 2.5 (2.0 to 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, rs799454(G) was associated with stroke/transient ischaemic attack in SLE (OR 1.7 (1.3 to 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/MI 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.

Place, publisher, year, edition, pages
2018. Vol. 77, no 7, p. 1063-1069
Keywords [en]
rheumatoid arthritis
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:liu:diva-149018DOI: 10.1136/annrheumdis-2017-212614ISI: 000438037000029PubMedID: 29514802OAI: oai:DiVA.org:liu-149018DiVA, id: diva2:1223452
Available from: 2018-06-25 Created: 2018-06-25 Last updated: 2018-08-17

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Frodlund, MartinaSjöwall, Christopher
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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDepartment of Rheumatology
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