Interdonor variability of platelet response to thrombin receptor activation: influence of PlA2 polymorphism
| Autor: | Francine Rendu, Martine Aiach, Emmanuel Arnaud, Jean-Noël Fiessinger, Veronique Pingault, Maria Krenn, Dominique Lasne |
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| Rok vydání: | 1997 |
| Předmět: |
Blood Platelets
chemistry.chemical_classification medicine.medical_specialty Polymorphism Genetic Genotype Platelet Glycoprotein GPIIb-IIIa Complex Hematology Biology Peptide Fragments Enzyme Thrombin Endocrinology chemistry Cell surface receptor Internal medicine Thrombin receptor Plasminogen Activator Inhibitor 2 medicine Humans Receptors Thrombin Platelet Secretion Dense granule Allele medicine.drug |
| Zdroj: | British Journal of Haematology. 99:801-807 |
| ISSN: | 0007-1048 |
| DOI: | 10.1046/j.1365-2141.1997.4973300.x |
| Popis: | Considering that platelet response to thrombin receptor activation might be critical for the development of arterial thrombosis, we measured the dense granule release under stimulation by the thrombin receptor activating peptide (TRAP) in a series of 102 healthy volunteers. The threshold TRAP concentration which initiated a secretion ranged from 3 to 20 microM. A good concordance (79%, k=0.677) between two tests performed at a 1 month interval indicated that platelet response to thrombin receptor activation was characteristic of each individual donor. Since the threshold concentration required to initiate secretion corresponded to the threshold concentration which induced a biphasic aggregation, all volunteers were genotyped for the PlA2 polymorphism, the Pro33 variant of GPIIIa. Platelets from subjects with the PlA2 polymorphism required higher TRAP concentrations to aggregate than those from subjects with no PlA2 allele (P=0.0012). However, they also required a higher ADP concentration to aggregate. In order to exclude any influence of GPIIIa polymorphism on TRAP-induced secretion, we studied the variability of platelet response to TRAP among the 77 individuals with no PlA2 allele, and found the same interdonor variability with the same distribution of threshold TRAP concentrations as for the 102 individuals. The results suggest that (i) platelet secretion in response to thrombin receptor activation could be a genetically controlled phenotype independent of the GPIIIa polymorphism; (ii) the PlA2 polymorphism is associated with platelet hypoaggregability. |
| Databáze: | OpenAIRE |
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