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  • Association of chemokine CXC ligand 12 gene polymorphism (rs1746048) with cardiovascular mortality in patients with rheumatoid arthritis: results from the Norfolk Arthritis Register

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Association of chemokine CXC ligand 12 gene polymorphism (rs1746048) with cardiovascular mortality in patients with rheumatoid arthritis: results from the Norfolk Arthritis Register
  1. Ibrahim Ibrahim1,
  2. Jennifer Humphreys1,
  3. Ibtisam Mokhtar1,
  4. Tarnya Marshall2,
  5. Suzanne Verstappen1,
  6. Deborah Symmons1,3,
  7. Sebastien Viatte1,
  8. Anne Barton1,2,
  9. Darren Plant1,3
  1. 1 Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  2. 2 Department of Rheumatology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
  3. 3 NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  1. Correspondence to Dr Darren Plant, Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Room 2.906, Stopford Building, Oxford Road, Manchester M13 9PT, UK; darren.plant{at}manchester.ac.uk

http://dx.doi.org/10.1136/annrheumdis-2015-207851

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    Patients with rheumatoid arthritis (RA) are at increased risk of premature mortality, with cardiovascular disease (CVD) forming the primary cause.1

    Previous studies have identified correlations between genetic polymorphisms located both inside2 and outside3 the human leucocyte antigen locus with increased risk of CVD morbidity and mortality, independent of traditional CVD risk factors.

    A recent genome-wide association study identified a genetic variant (rs1746048) proximal to the CXCL12 gene on chromosome 10q11.21, that is strongly associated with coronary artery disease (p=8.1×10−9),4 increased carotid intimal–medial thickness5 and plasma levels of CXCL12.6 Several studies have highlighted an important role for CXCL12 in RA by demonstrating increased levels of CXCL12 in synovial fluid, as well as upregulation of CXCL12 mRNA in synovial fibroblasts, which may contribute to sustained inflammation.7 However, a large study of Spanish patients with established RA did not detect an association with CVD outcome and a …

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    Footnotes

    • Contributors DP conceived the study, designed the study, cleaned the data, performed statistical analysis and drafted and revised the manuscript. II cleaned the data, performed statistical analysis and drafted and revised the manuscript. JH, IM, TM, SVe, DS and SVi designed the study and drafted and revised the manuscript. AB conceived the study, designed the study, designed the data collection tools, monitored data collection and drafted and revised the manuscript. AB is the guarantor. All authors have read and approved the final manuscript for publication.

    • Funding This work was funded by a core programme grant from Arthritis Research UK (grant ref: 20385) and by the National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit.

    • Disclaimer The views expressed are those of the authors’, and not necessarily those of the NHS, the NIHR or the Department of Health.

    • Competing interests None declared.

    • Ethics approval Norwich Local Research Ethics Committee.

    • Provenance and peer review Not commissioned; externally peer reviewed.