title: Rheumatoid arthritis susceptibility genes associate with lipid levels in patients with rheumatoid arthritis.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, West Midlands DY1 2HQ, UK.
authors.forename: Tracey E
authors.initials: TE
authors.lastname: Toms
authors.forename: Vasileios F
authors.initials: VF
authors.lastname: Panoulas
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Smith
authors.forename: Karen M J
authors.initials: KM
authors.lastname: Douglas
authors.forename: Giorgos S
authors.initials: GS
authors.lastname: Metsios
authors.forename: Antonios
authors.initials: A
authors.lastname: Stavropoulos-Kalinoglou
authors.forename: George D
authors.initials: GD
authors.lastname: Kitas
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000235:genetics*; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000235:genetics; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008055:Lipids; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D047990:TNF Receptor-Associated Factor 1; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22