The von Willebrand factor (VWF) may be causally associated with coronary heart disease (CHD) or merely be a marker of endothelial damage. The G allele of the -1793 C/G promoter polymorphism in the VWF gene has been associated with higher plasma levels of VWF. To investigate whether VWF has a causal role in CHD, we designed a case-cohort study, including 352 subjects with CHD and a random cohort (n = 736), and prospectively examined the association of the -1793 C/G polymorphism with CHD in subjects with and without advanced atherosclerosis. All subjects were ≤75 years of age and participating in the population-based Rotterdam Study. Atherosclerosis was assessed by the ankle-arm index. Among subjects with advanced atherosclerosis, heterozygous and homozygous carriers of the G allele had a 3.5 (1.2-10.2) and 1.5 (0.4-5.7) fold increased risk of CHD respectively, compared with C/C homozygotes. The hazard ratio was 2.6 (1.0-6.8) for carriers of at least one copy of the G allele versus non-carriers. No associations were found in the absence of advanced atherosclerosis. In conclusion, this study suggests that the G allele of the -1793 C/G polymorphism in the VWF gene is associated with an increased risk of CHD, but only in subjects with advanced atherosclerosis.

Aetiology, Epidemiology, Genetics of thrombosis and haemostasis, Vascular disease, Von Willebrand factor,
British Journal of Haematology
Erasmus MC: University Medical Center Rotterdam

Meer, I.M, Brouwers, G.J, Bulk, S, Leebeek, F.W.G, van der Kuip, D.A.M, Hofman, A, … Gómez García, E.B. (2004). Genetic variability of von Willebrand factor and risk of coronary heart disease: The Rotterdam Study. British Journal of Haematology, 124(3), 343–347. doi:10.1046/j.1365-2141.2003.04776.x