title: Identification of functional polymorphisms of the thromboxane A2 receptor gene in healthy volunteers.
abstract: Thromboxane A2 receptor (TP) is an important actor in vascular physiology and plays a crucial role in the platelet activation process. Genetic polymorphisms of the gene coding for the TP have been described, but their impacts on platelet function tests are unknown. The aim of this study was to investigate the relationship between genetic polymorphisms of the coding sequence of the TP gene and platelet function tests. We investigated 100 healthy volunteers twice, one week apart by performing platelet aggregation and secretion tests. We sequenced the coding region of the TP gene and confronted the genetic variants with the phenotypic results. We identified five single nucleotide polymorphisms (SNP); one of them, T1712C, replaces Leu by Pro at position 133 of the isoform beta of the TP. Homozygosity for the minor allele of the C795T, C924T or the G1686A SNP was associated with a decreased expression of CD62P when platelets were stimulated with the TP agonist U46619. As C795T and C924T have been linked to clinical disorders in which TxA2 plays a key role, the possible role of the G1686A and T1712C SNP should also be examined in selected diseases.
authors.affiliation: INSERM Unité 765, Hôpital Européen Georges Pompidou (AP-HP), Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
authors.forename: Sophie
authors.initials: S
authors.lastname: Gandrille
authors.forename: Véronique
authors.initials: V
authors.lastname: Remones
authors.forename: Annabelle
authors.initials: A
authors.lastname: Dupont
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Reny
authors.forename: Martine
authors.initials: M
authors.lastname: Aiach
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
mesh_terms: D000293:Adolescent; D000328:Adult; D005434:Flow Cytometry; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008957:Models, Genetic; D019007:P-Selectin / Q000096:biosynthesis; D010641:Phenotype; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics*
chemical_list: D019007:P-Selectin; D044244:Receptors, Thromboxane A2, Prostaglandin H2