The influence of platelet collagen receptor polymorphisms in hemostasis and thrombotic disease.
Extracellular collagens modulate the rate of platelet activation and thereby markedly influence hemostasis and thrombosis. Platelet receptors for collagens, such as the integrin alpha(2)beta(1), 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 GPIbalpha and integrin alpha(2) polymorphisms, but these discrepancies will be resolved once there is better standardization of clinical studies. There is already substantial evidence that GPIbalpha VNTR A or B alleles, the GPIbalpha-5C allele, and integrin alpha(2) allele 1 (T(807)) 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.
Kunicki
Thomas J
TJ
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis, The Scripps Research Institute, La Jolla, CA 92037, USA. tomk@scripps.edu
D015703:Antigens, CD / Q000235:genetics; D001792:Blood Platelets / Q000737:chemistry* / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D039421:Integrin alpha2; D016023:Integrins / Q000235:genetics* / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D038981:Receptors, Collagen; D020080:Tandem Repeat Sequences; D013927:Thrombosis / Q000097:blood / Q000235:genetics*; D014842:von Willebrand Diseases / Q000097:blood
D015703:Antigens, CD; D018955:CD36 Antigens; D039421:Integrin alpha2; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI; D003094:Collagen