Genetic variability of von Willebrand factor and risk of coronary heart disease: the Rotterdam Study.

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.