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. OBJECTIVES: 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.
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. OBJECTIVES: 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: Ahmad H Mufti; Kenichi Ogiwara; Laura L Swystun; Jeroen C J Eikenboom; Ulrich Budde; Wilma M Hopman; Christer Halldén; Jenny Goudemand; Ian R Peake; Anne C Goodeve; David Lillicrap; Daniel J Hampshire Journal: Blood Adv Date: 2018-07-10
Authors: Jill M Johnsen; Paul L Auer; Alanna C Morrison; Shuo Jiao; Peng Wei; Jeffrey Haessler; Keolu Fox; Sean R McGee; Joshua D Smith; Christopher S Carlson; Nicholas Smith; Eric Boerwinkle; Charles Kooperberg; Deborah A Nickerson; Stephen S Rich; David Green; Ulrike Peters; Mary Cushman; Alex P Reiner Journal: Blood Date: 2013-05-20 Impact factor: 22.113
Authors: Weihong Tang; Mary Cushman; David Green; Stephen S Rich; Leslie A Lange; Qiong Yang; Russell P Tracy; Geoffrey H Tofler; Saonli Basu; James G Wilson; Brendan J Keating; Lu-Chen Weng; Herman A Taylor; David R Jacobs; Joseph A Delaney; Cameron D Palmer; Taylor Young; James S Pankow; Christopher J O'Donnell; Nicholas L Smith; Alexander P Reiner; Aaron R Folsom Journal: Am J Hematol Date: 2015-04-01 Impact factor: 13.265
Authors: Peter Willeit; Alexander Thompson; Thor Aspelund; Ann Rumley; Gudny Eiriksdottir; Gordon Lowe; Vilmundur Gudnason; Emanuele Di Angelantonio Journal: PLoS One Date: 2013-02-07 Impact factor: 3.240