Influence of P2Y12 polymorphisms on platelet activity but not ex-vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects.
Blood Coagul Fibrinolysis
; 26(8): 874-81, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26083990
ABSTRACT
Activation of platelet implicated a series of signal conduction including outside-in and inside-out related receptor-mediated signaling pathways. Ticagrelor is the first reversible P2Y12 receptor antagonist that exhibits rapid antiplatelet effect. Given that platelet aggregation varies among individuals, genetic polymorphisms in P2Y12 and subsequent signal molecular such as the G-protein beta 3 subunit (GNB3) are supposed to influence the antiplatelet effect of ticagrelor. The aim of this study was to determine whether genetic polymorphisms in P2Y12 and GNB3 genes influence ex-vivo antiplatelet activity of ticagrelor in healthy Chinese subjects. A total of 196 healthy Chinese male individuals were recruited. ADP-induced platelet aggregation was determined by using light transmittance aggregometry at baseline and after incubation of the platelet-rich plasma with 15 and 50âµmol/l ticagrelor, respectively. Nine single-nucleotide polymorphisms (SNPs) in P2Y12 and the GNB3 rs5443 polymorphism were genotyped by PCR-direct sequencing. P2Y12 haplotypes were inferred. Baseline platelet aggregation was increased in carriers of the common alleles of P2Y12 SNPs (rs1907637, rs2046934, and rs6809699) and rs6787801 TC heterozygotes (Pâ<â0.05 for all). Results of the haplotype analyses were consistent with those of the single SNPs. Ticagrelor at both concentrations of 15 and 50âµmol/l decreased ADP-induced platelet aggregation significantly (Pâ<â0.05, respectively). Neither single SNPs nor haplotypes of P2Y12 affected ticagrelor-induced ex-vivo inhibition of platelet aggregation. P2Y12 and GNB3 polymorphisms have no effect on the ex-vivo antiplatelet activity of ticagrelor in healthy Chinese male subjects.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Adenosina
/
Proteínas Heterotriméricas de Ligação ao GTP
/
Polimorfismo de Nucleotídeo Único
/
Receptores Purinérgicos P2Y12
/
Antagonistas do Receptor Purinérgico P2Y
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article