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Extended report
Rheumatoid arthritis susceptibility genes associate with lipid levels in patients with rheumatoid arthritis
  1. Tracey E Toms1,2,
  2. Vasileios F Panoulas1,
  3. Jacqueline P Smith1,
  4. Karen M J Douglas1,
  5. Giorgos S Metsios1,3,
  6. Antonios Stavropoulos-Kalinoglou1,3,
  7. George D Kitas1,2
  1. 1Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, West Midlands DY1 2HQ, UK
  2. 2Arthritis Research UK Epidemiology Unit, Manchester University, Manchester M13 9PT, UK
  3. 3School of Sport, Performing Arts and Leisure, University of Wolverhampton, Walsall WS1 3BD, UK
  1. Correspondence to Professor George D Kitas, Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Pensnett Road, Dudley, West Midlands DY1 2HQ, UK; gd.kitas{at} or g.d.kitas{at}


Introduction Rheumatoid arthritis (RA), a systemic inflammatory disease with complex genetic aetiology, associates with excess cardiovascular morbidity and mortality. Dyslipidaemia, a major cardiovascular risk factor has been reported to predate the onset of RA, thus suggesting a potential genetic link between the two conditions. The authors assessed whether RA susceptibility genes associate with the presence of dyslipidaemia in RA patients.

Methods 400 well-characterised RA patients were included in this cross-sectional study. Fasting lipid profile (total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, apolipoproteins (ApoA and ApoB) and lipoprotein (a)) and four RA susceptibility genes (PTPN22, TRAF1/C5, STAT4 and human leucocyte antigen shared epitope (HLA-SE)) were assessed and associations were sought in both univariate and multivariate analyses.

Results Following adjustment for age, sex and erythrocyte sedimentation rate, the G allele of TRAF1/C5 associated with lower total cholesterol (p=0.010), LDL (p=0.022) and ApoB (p=0.014); one or more copies of the shared epitope associated with lower ApoA (p=0.035) and higher ApoB:ApoA ratio (p=0.047); while STAT4 TT homozygotes had higher lipoprotein (a) (p=0.004).

Conclusions RA susceptibility genes (TRAF1/C5, STAT4 and HLA-DRB1-SE) may be involved in the regulation of lipid metabolism in RA patients, thus contributing to cardiovascular disease (CVD) risk and adverse outcome. If these findings are replicated, such genotyping could be used to identify and target for prevention those RA patients most at risk of CVD. It will also be interesting to study the association of these genes with lipid levels in the general population and identify mechanisms to explain the link.

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  • Funding This work was supported by an Arthritis Research UK clinical research fellowship grant (grant no 18848 to TET), and an Arthritis Research UK infrastructure support grant (grant no 17682, given to the Dudley Group of Hospitals NHS Foundation Trust, Department of Rheumatology). VFP was supported by a PhD scholarship from the Empirikion Foundation, Athens, Greece.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Black Country Ethics Committee, UK.

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