von Willebrand factor plasma levels, genetic variations and coronary heart disease in an older population

Journal of Thrombosis and Haemostasis : JTH
J E van LoonMoniek P M de Maat

Abstract

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. 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. 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. 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 p...Continue Reading

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