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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:14.)
© 2002 American Heart Association, Inc.

Brief Reviews

The Influence of Platelet Collagen Receptor Polymorphisms in Hemostasis and Thrombotic Disease

Thomas J. Kunicki

From The Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis of the Department of Molecular and Experimental Medicine and the Department of Vascular Biology, The Scripps Research Institute, La Jolla, Calif.

Address correspondence to Thomas J. Kunicki, PhD, Associate Professor, Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, Maildrop: MEM 150, La Jolla, CA 92037. E-mail tomk{at}scripps.edu

Extracellular collagens modulate the rate of platelet activation and thereby markedly influence hemostasis and thrombosis. Platelet receptors for collagens, such as the integrin ₂ß₁, platelet glycoprotein (GP) VI or, indirectly, the GPIb complex, are unexploited targets of pharmacological control, and polymorphisms of these receptors have recently become factored into the genetic risk for thrombosis. Seemingly contradictory findings already exist with regard to the contribution of GPIb and integrin ₂ polymorphisms, but these discrepancies will be resolved once there is better standardization of clinical studies. There is already substantial evidence that GPIb VNTR A or B alleles, the GPIb-5C allele, and integrin ₂ allele 1 (T₈₀₇) each contribute to increased risk for morbidity in thrombotic disease. However, larger, prospective genetic and epidemiological studies are needed to clarify the role of each of these polymorphisms, the contribution of other platelet receptor polymorphisms, and the synergistic effects of combinations of these factors. In addition, in vitro studies that establish the functional relevance of these polymorphisms will provide sound biological explanations for the results of clinical correlation studies.

Key Words: platelet • collagen • integrin • GPVI • thrombosis

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