Genetic factors underlying differential blood platelet sensitivity to inhibitors.
Blood platelets are not only the primary defence mechanism involved in physiological hemostasis, but also their disorders constitute a crucial risk factor in arterial thrombosis. As arterial thrombi are composed of predominantly platelets formed under conditions of elevated shear stress at sites of atherosclerotic vascular injury and disturbed blood flow, the prevention of arterial thrombosis has been for years the main target for antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. Some clinical studies have indicated that platelet glycoprotein polymorphisms are genetic factors contributing to arterial thrombosis. In spite of some discrepancies between different studies, there is substantial evidence that the integrin beta3 P1(A2) allele, the variants GPIbalpha Met145 and GPIbalpha (-5C) haplotype or the integrin alpha2 haplotype 1 (807T) each contribute to the risk for and morbidity of thrombotic disease. In this article, we reviewed a role of the aforementioned polymorphisms in modulating platelet function and platelet response to inhibitors. The paper focuses on the association between Pl(A1/A2) polymorphism and sensitivity (or resistance) to aspirin and the inhibitory efficacy of GPIIb-IIIa antagonists. Additionally, a potential role of 807C/T polymorphism (GPIa), polymorphisms of GPIb and platelet purinoreceptor P2Y12 in affecting platelet sensitivity to blocking agents is discussed.
Rozalski
Marcin
M
Department of Hemostasis and Hemostatic Disorders, Medical University of Łódź, Zeromskiego 113, PL 90-549 Łódź, Poland.
Boncler
Magdalena
M
Luzak
Boguslawa
B
Watala
Cezary
C
D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000502:physiology; D010597:Pharmacogenetics; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000235:genetics; D011110:Polymorphism, Genetic
D038982:Integrin alpha2beta1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex