The role of platelet collagen receptor (glycoprotein Ia/IIa; integrin alpha2 beta1) polymorphisms in thrombotic disease.
Differences in rates of platelet activation induced by extracellular matrix components such as collagens markedly influence normal hemostasis and the pathologic outcome of thrombosis. Thus, platelet collagen receptors, the integrin alpha2beta1, glycoprotein VI, and the glycoprotein Ib complex, represent unexploited targets of pharmacologic control. Polymorphisms of these receptors are now understood as factors that potentially contribute to thrombotic risk. There is substantial evidence that the GPIbalpha variable number of tandem repeats A or B alleles, the -5C allele of GPIbalpha, and the integrin alpha2 allele 1 (T807) each contribute to risk for and morbidity from thrombotic disease. The extent of their individual contributions is disputed. More well-designed, large, prospective, genetic and epidemiologic studies are needed to clarify the role of these and other platelet receptor polymorphisms, and additional in vitro studies are needed to provide a sound biologic explanation for the outcomes of clinical correlations.
Kunicki
T J
TJ
The Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis of the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA. tomk@scripps.edu
D001792:Blood Platelets / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics* / Q000502:physiology; D008954:Models, Biological; D010973:Platelet Adhesiveness; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic; D038981:Receptors, Collagen; D013927:Thrombosis / Q000209:etiology / Q000235:genetics*; D014158:Transcription, Genetic
D016023:Integrins; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI; D003094:Collagen