Effect of the 807 c/t polymorphism in glycoprotein ia on blood platelet reactivity.
The 807 C/T dimorphism in the GPIa gene has been shown to affect GPIaIIa receptor density, which can affect platelet adhesiveness to collagens. In this work, we studied platelet function mediated by GPIaIIa. The 807 T/T genotype was associated with increased platelet adhesion to monomeric collagen after activation with ADP, but not following activation with thrombin and U46619. Adhesion to fibrillar collagen and PFA-100 closure time were not different between carriers of the C/C and T/T genotypes. Also, to monitor the role of the 807 C/T polymorphism in the sensitivity to platelet antagonists, anti-GPIaIIa monoclonal antibodies (Gi9) were used. Irrespective of the 807 C/T genotype, Gi9 inhibited the ADP-induced platelet adhesion to the monomeric collagen-coated surface stronger than adhesion evoked by thrombin. Moreover, Gi9 significantly inhibited platelet adhesion to both monomeric and fibrillar collagen in 807 T/T carriers, whereas in 807 C/C subjects, Gi9 blocked only adhesion to monomeric collagen. Our results indicate that the 807 T/T genotype is related to increased platelet activation induced by ADP and higher platelet sensitivity to GPIaIIa antagonists.
Luzak
Boguslawa
B
Department of Hemostasis and Hemostatic Disorders, Medical University of Łódź, ul. Narutowicza 96, PL-90-141 Łódź, Poland.
Golanski
Jacek
J
Rozalski
Marcin
M
Watala
Cezary
C
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000378:metabolism; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers; D004586:Electrophoresis; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000235:genetics*; D011044:Poland; D011110:Polymorphism, Genetic / Q000235:genetics*; D013917:Thrombin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D006023:Glycoproteins; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D013917:Thrombin