title: Associations between APOE genotypes and disease susceptibility, joint damage and lipid levels in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Apolipoprotein E (APOE) genotypes are associated with cardiovascular disease (CVD) and lipid levels. In rheumatoid arthritis (RA), an association has been found with disease activity. We examined the associations between APOE genotypes and disease susceptibility and markers of disease severity in RA, including radiographic joint damage, inflammatory markers, lipid levels and cardiovascular markers.
  
  
  METHODS
  A Norwegian cohort of 945 RA patients and 988 controls were genotyped for two APOE polymorphisms. We examined longitudinal associations between APOE genotypes and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as hand radiographs (van der Heijde Sharp Score(SHS)) in 207 patients with 10 year longitudinal data. Lipid levels, cardiovascular markers and history of CVD were compared across genotypes in a cross sectional study of 136 patients. Longitudinal radiological data of cohorts from Lund and Leiden were available for replication. (N = 935, with 4799 radiographs).
  
  
  RESULTS
  In the Norwegian cohort, associations between APOE genotypes and total cholesterol (TC) and low-density lipoproteins (LDL) were observed (ε2 < ε3/ε3 < ε4, p = 0.03 and p = 0.02, respectively). No association was present for acute phase reactant or CVD markers, but a longitudinal linear association between APOE genotypes and radiographic joint damage was observed (p = 0.007). No association between APOE genotypes and the severity of joint destruction was observed in the Lund and Leiden cohorts, and a meta- analysis combining all data was negative.
  
  
  CONCLUSIONS
  APOE genotypes are associated with lipid levels in patients with RA, and may contribute to dyslipidemia in some patients. APOE genotypes are not consistently associated with markers of inflammation or joint destruction in RA.
authors.affiliation: Department of Medical Genetics, University of Oslo and Oslo University Hospital, Ullevål, Oslo, Norway. marthemaehlen@gmail.com
authors.forename: Marthe T
authors.initials: MT
authors.lastname: Maehlen
authors.forename: Sella A
authors.initials: SA
authors.lastname: Provan
authors.forename: Diederik P C
authors.initials: DP
authors.lastname: de Rooy
authors.forename: Annette H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
authors.forename: Annemarie
authors.initials: A
authors.lastname: Krabben
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
authors.forename: Elisabet
authors.initials: E
authors.lastname: Lindqvist
authors.forename: Anne Grete
authors.initials: AG
authors.lastname: Semb
authors.forename: Till
authors.initials: T
authors.lastname: Uhlig
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Inger Lise
authors.initials: IL
authors.lastname: Mero
authors.forename: Inge C
authors.initials: IC
authors.lastname: Olsen
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood / Q000150:complications / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D001175:Arthrography; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D003710:Demography; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007596:Joints / Q000473:pathology*; D008055:Lipids / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009664:Norway
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D002097:C-Reactive Protein