Homozygosity for 807 T polymorphism in alpha(2) subunit of platelet alpha(2)beta(1) is associated with increased risk of cardiovascular mortality in high-risk women.

Background: Platelet adhesion to collagen is the initial step in both hemostasis and thrombosis; this adhesion is mediated by alpha(2)beta(1) on the surface of platelet membranes. An 807 C to T single nucleotide exchange polymorphism close to the gene coding for the alpha(2) subunit of alpha(2)beta(1) is associated with the density of alpha(2)beta(1) on the platelet membrane.

Methods And Results: We studied the relation of the alpha(2)beta(1) 807 C/T genotype to cardiovascular mortality in a prospective cohort study of 12 239 women who were invited for the breast cancer screening program of Utrecht, the Netherlands. The initial age was between 52 and 67 years. Women were followed on vital status between 1976 and 1995 (168 513 women-years). Data were analyzed by using a nested case-control design. The alpha(2)beta(1) 807 C/T genotype was not associated with cardiovascular mortality in the total population: the rate ratio for cardiovascular mortality in 807 TT homozygotes compared with 807 CC wild types was 1.2 (95% CI 0.8 to 1.7). However, the alpha(2)beta(1) 807 T polymorphism was associated with an increased risk of cardiovascular mortality in women who smoked or in women who had indications of compromised endothelium, such as diabetes and microalbuminuria. In those who were exposed to >/=2 of these factors, the risk ratio (95% CI) between alpha(2)beta(1) 807 TT homozygotes and 807 CC wild types was 14.1 (5.0 to 39.9).

Conclusions: alpha(2)beta(1) 807 TT homozygosity, coding for increased alpha(2)beta(1) density on the platelet membrane, is associated with an increased risk of cardiovascular mortality in those women with indications of compromised endothelium.