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(Circulation. 2000;102:1645.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Homozygosity for 807 T Polymorphism in ₂ Subunit of Platelet ₂ß₁ Is Associated With Increased Risk of Cardiovascular Mortality in High-Risk Women

Mark Roest, PhD; Jan Dirk Banga, MD, PhD; Diederick E. Grobbee, MD, PhD; Philip G. de Groot, PhD; Jan J. Sixma, MD, PhD; Mariëlle J. Tempelman, BSc; Yvonne T. van der Schouw, PhD

From the Julius Center for Patient Oriented Research (M.R., D.E.G., Y.T.v.d.S.), the Department of Hematology (M.R., P.G.d.G., J.J.S., M.J.T.), Graduate School of Biomembranes, and the Department of Internal Medicine (M.R., J.D.B.), Utrecht University Medical School, Utrecht, the Netherlands.

Correspondence to Mark Roest, MSc, Julius Center for Patient Oriented Research, Utrecht University Medical School, Heidelberglaan 100, 3584 CX Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands.

Background—Platelet adhesion to collagen is the initial step in both hemostasis and thrombosis; this adhesion is mediated by ₂ß₁ on the surface of platelet membranes. An 807 C to T single nucleotide exchange polymorphism close to the gene coding for the ₂ subunit of ₂ß₁ is associated with the density of ₂ß₁ on the platelet membrane.

Methods and Results—We studied the relation of the ₂ß₁ 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 ₂ß₁ 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 ₂ß₁ 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 ₂ß₁ 807 TT homozygotes and 807 CC wild types was 14.1 (5.0 to 39.9).

Conclusions—₂ß₁ 807 TT homozygosity, coding for increased ₂ß₁ density on the platelet membrane, is associated with an increased risk of cardiovascular mortality in those women with indications of compromised endothelium.

Key Words: platelets • genes • cardiovascular diseases • women

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