Association of a rheumatoid arthritis susceptibility variant at the CCL21 locus with premature mortality in inflammatory polyarthritis patients

Farragher, TM, Plant, D, Flynn, E, Eyre, S, Bunn, D, Thomson, W, Symmons, D and Barton, A (2010) Association of a rheumatoid arthritis susceptibility variant at the CCL21 locus with premature mortality in inflammatory polyarthritis patients. Arthritis Care & Research, 62 (5). pp. 676-682. ISSN 2151-4658

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Abstract

Objective To investigate whether recently identified rheumatoid arthritis (RA) susceptibility loci are also associated with disease severity, specifically all-cause and cardiovascular disease (CVD) mortality, in patients with inflammatory polyarthritis (IP). Methods Subjects with recent-onset IP were recruited from the Norfolk Arthritis Register. Seventeen RA susceptibility single-nucleotide polymorphisms (SNPs) were tested using Sequenom MassArray iPLEX chemistry. Vital status was ascertained from central records. The association of SNP allele carriage with mortality risk was assessed using Cox proportional hazards models after adjusting by sex. The mortality risks of those SNP alleles found to be associated were then stratified by baseline anti–citrullinated peptide (anti-CCP) antibody and shared epitope (SE) status. Results All SNPs were successfully genotyped in 2,324 IP subjects. The presence of 2 copies of the risk allele rs2812378 mapping to the CCL21 gene predicted all-cause mortality (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.04–1.87), whereas risk allele carriage also predicted increased CVD mortality (HR 1.33, 95% CI 1.01–1.75). The highest mortality risks were seen in anti-CCP antibody–positive subjects with 2 copies of the CCL21 risk alleles and 2 copies of the SE (all-cause HR 3.20, 95% CI 1.52–6.72; CVD HR 3.73, 95% CI 1.30–10.72). Conclusion In this large study, we found that carriage of CCL21 risk alleles was associated with premature mortality in IP independently of anti-CCP antibody and SE status. Interestingly, CCL21 expression has been reported in atherosclerotic plaques supporting the thesis that the increased CVD mortality in IP patients may be mediated by shared inflammatory mechanisms.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: Rhiannon Harvey
Date Deposited: 07 Mar 2012 12:01
Last Modified: 05 Dec 2018 15:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/38007
DOI: 10.1002/acr.20208

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