title: TRAF1/C5 polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies.
abstract: BACKGROUND
  Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.
  
  
  METHODS
  615 RA patients from the Leiden Early Arthritis Clinic (EAC) (mean follow-up 7.6 years) were genotyped for rs10818488. In addition 5634 persons enrolled in the PROspective Study of Pravastatin in the Elderly at Risk (mean follow-up 3.2 years) were genotyped for rs2416808 (R(2) >0.99 with rs10818488). The life/death status was determined and for the deceased persons the cause of death was ascertained. Cox proportional hazards and regression models were used to assess hazard ratios (HR) and 95% confidence intervals (CI).
  
  
  RESULTS
  Seventy-seven RA patients died. The main death causes in RA patients were cardiovascular diseases (37.7%), cancer (28.6%) and death due to infections (9.1%). No association was observed between the rs10818488 susceptible genotype AA and cardiovascular mortality (HR 1.08 95%CI 0.54 to 2.15) and all-cause mortality (HR 0.81 95%CI 0.27 to 2.43). Similar findings were observed for rs2416808 susceptible genotype GG in the non-RA cohort (HR 0.99; 95%CI 0.79 to 1.25 and HR 0.89; 95%CI 0.64 to 1.25, respectively).
  
  
  CONCLUSIONS
  The TRAF1/C5 region is not associated with an increased mortality risk.
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. jessicavannies@gmail.com
authors.forename: Jessica A B
authors.initials: JA
authors.lastname: van Nies
authors.forename: Rute B
authors.initials: RB
authors.lastname: Marques
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.forename: Zuzana
authors.initials: Z
authors.lastname: de Jong
authors.forename: Fina A S
authors.initials: FA
authors.lastname: Kurreeman
authors.forename: Rene E M
authors.initials: RE
authors.lastname: Toes
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Annette H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000401:mortality*; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D015897:Comorbidity; D003182:Complement C5 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009369:Neoplasms / Q000401:mortality; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D015996:Survival Rate; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*
chemical_list: D003182:Complement C5; D047990:TNF Receptor-Associated Factor 1