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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. 1Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  2. 2Department of Rheumatology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
  3. 3NIHR 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}

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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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