title: von Willebrand factor plasma levels, genetic variations and coronary heart disease in an older population.
abstract: BACKGROUND
  High von Willebrand factor (VWF) levels are associated with an increased risk of coronary heart disease (CHD). However, it remains unclear whether VWF is causally related to the occurrence of CHD or primarily mirrors endothelial dysfunction, which predisposes to atherosclerosis and subsequent CHD.
  
  
  OBJECTIVE
  Because VWF is largely determined by genetic factors, we investigated whether VWF antigen levels (VWF:Ag) and the risk of CHD are affected by common variations in the VWF gene.
  
  
  METHODS
  We included 7002 participants (≥ 55 years) from the large prospective population-based Rotterdam Study in the discovery cohort. The extension cohort of the Rotterdam Study, consisting of 3011 participants, was used as a replication cohort. We determined VWF:Ag levels and genotype data of 38 single-nucleotide polymorphisms (SNPs) in VWF. Subsequently, hazard ratios for CHD were calculated and genetic analyses were performed to assess the relationship between SNPs, VWF:Ag levels and CHD risk.
  
  
  RESULTS
  We identified and replicated three SNPs that were associated with VWF:Ag: rs216321 (β = 0.10 [95% confidence interval, CI, 0.06;0.13]) (Ala852Gln), rs1063856 (β = 0.05 [95% CI 0.03;0.07]) (Thr789Ala) and rs2283333 (β = 0.09 [95% CI 0.05;0.21]) (intron 15). However, genetic polymorphisms in the VWF gene were not associated with the risk of CHD.
  
  
  CONCLUSIONS
  In this study we have shown that genetic variations in VWF strongly affect VWF plasma levels, but are not associated with the risk of CHD. Our findings therefore do not support a strong causal relationship between VWF and CHD in elderly individuals of ≥ 55 years, but suggest that VWF is primarily a marker of CHD.
authors.affiliation: Department of Hematology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
authors.forename: J E
authors.initials: JE
authors.lastname: van Loon
authors.forename: M
authors.initials: M
authors.lastname: Kavousi
authors.forename: F W G
authors.initials: FW
authors.lastname: Leebeek
authors.forename: J F
authors.initials: JF
authors.lastname: Felix
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: J C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: M P M
authors.initials: MP
authors.lastname: de Maat
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor