HLA-DRB1 haplotypes predict cardiovascular mortality in inflammatory polyarthritis independent of CRP and anti-CCP status

Sharma, Seema, Plant, Darren, Bowes, John, Macgregor, Alex ORCID: https://orcid.org/0000-0003-2163-2325, Verstappen, Suzanne, Barton, Anne and Viatte, Sebastien (2022) HLA-DRB1 haplotypes predict cardiovascular mortality in inflammatory polyarthritis independent of CRP and anti-CCP status. Arthritis Research & Therapy, 24. ISSN 1478-6354

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Abstract

Background: Haplotypes defined by amino acids at HLA-DRB1 positions 11, 71 and 74 associated with susceptibility to rheumatoid arthritis (RA) are associated with radiological outcome, anti-TNF response and all cause-mortality in RA. RA is associated with cardiovascular (CV) morbidity and mortality, but the increased prevalence of risk factors of CV disease in RA only partially explains this association. The aim of this study was to investigate whether amino acids at positions 11, 71 and 74 of HLA-DRB1 are associated with cardiovascular (CV) mortality in inflammatory polyarthritis (IP). Methods: The Norfolk Arthritis Register (NOAR) is an incidence register of IP: recruitment 1990–2007, final follow-up 2011. Two thousand five hundred fourteen patients had available genetic and mortality data. Amino acids at positions 11, 71 and 74 of HLA-DRB1 were determined. Univariate Cox proportional hazard models were applied to assess the association of genetic markers and both all-cause mortality and cardiovascular mortality. Results: Among 2514 participants, 643 (25.6%) died during the study, and 343 (53.3%) of these deaths were attributed to CV causes. One thousand six hundred fifty (65.6%) participants were female, 709 (32.3%) were anti-CCP-positive and the median age of participants was 54. HLA-DRB1 haplotypes associated with susceptibility to rheumatoid arthritis (RA) consistently show the same magnitude and direction of association for overall and CV mortality in IP. For example, the SEA-haplotype, associated with the lowest susceptibility to RA, and the best radiographic outcome, was found to be associated with decreased CV mortality (HR 0.67, 95% CI 0.47, 0.91, p=0.023). Mediation analysis revealed associations were independent of anti-CCP status. Conclusions: HLA-DRB1 haplotypes associated with susceptibility to RA also predispose to increased risk of CV mortality in IP, independent of known CV risk factors. Associations were independent of anti-CCP status, which suggests in the future, genetic factors will add to the prediction of risk of cardiovascular mortality beyond serological markers.

Item Type: Article
Additional Information: Funding information: Dr. Sharma was supported by the NIHR through an ACF post as part of the integrated academic training (IAT) programme. Dr. Bowes would like to acknowledge grant 34765 (BHF). The authors would like to acknowledge the core programme grant by Versus Arthritis.
Uncontrolled Keywords: anti-citrullinated protein antibodies,cardiovascular mortality,genetic biomarkers,hla-drb1,rheumatoid arthritis,rheumatology,immunology and allergy,immunology ,/dk/atira/pure/subjectarea/asjc/2700/2745
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
Faculty of Science > Research Groups > Norwich Epidemiology Centre
Faculty of Medicine and Health Sciences > Research Groups > Norwich Epidemiology Centre
Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health
Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine
Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research
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Depositing User: LivePure Connector
Date Deposited: 15 May 2023 16:30
Last Modified: 18 May 2023 08:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/92058
DOI: 10.1186/s13075-022-02775-0

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