Thromboxane A₂ Receptor Polymorphism in Association with Cerebral Infarction and its Regulation on Platelet Function

Title:Thromboxane A₂ Receptor Polymorphism in Association with Cerebral Infarction and its Regulation on Platelet Function

Volume: 12 Issue: 1

Author(s): Jiaxiang Shao, Yi Fu, Wanlin Yang, Jing Yan, Jing Zhao, Shengdi Chen and Weiliang Xia

Affiliation:

Keywords: Thromboxane A₂ receptor, cerebral infarction; single nucleotide polymorphism; integrin GPIIb/IIIa.

Abstract: Binding of thromboxane A₂ (TXA₂) to its receptor TXA₂R modulates thrombosis/hemostasis and plays a vital role in the pathogenesis of cerebral infarction (CI). In this study, we investigated the relationship between TXA₂R polymorphisms and CI in Chinese Han population and the effect on platelet function by these polymorphisms. Polymerase chain reaction and ligase detection reaction (PCR-LDR) was performed in 230 CI patients and 143 healthy volunteers to examine four single nucleotide polymorphisms (SNPs) in human TXA₂R gene (C795T, T924C and G1686A in the exon region, and rs768963 in the promoter region). We found that rs768963 polymorphism was significantly more frequent in the CI group than in the non-CI group and the T-T-G-T haplotype of C795T-T924C-G1686A-rs768963 was significantly less frequent in the CI subjects (0.238 versus 0.339; OR 0.617 [95%CI 0.444-0.856]). In the meantime, we constructed wild-type and mutant (C795T, G910A and T924C) eukaryotic expression plasmids, and transfected these plasmids into human embryonic kidney (HEK) 293T cells or Chinese hamster ovary (CHO) cells stably expressing human TXA₂R (GPb/a- CHO). C795T and T924C variants of TXA2R led to increased ligand binding-induced intracellular calcium influx and fibrinogen-integrin conjugation, while dominant negative mutant G910A abolished the signal enhancement. Together these data show that TXA2R polymorphisms may affect platelet function and the risk of developing cerebral ischemia.

Cite this article as:

Shao Jiaxiang, Fu Yi, Yang Wanlin, Yan Jing, Zhao Jing, Chen Shengdi and Xia Weiliang, Thromboxane A₂ Receptor Polymorphism in Association with Cerebral Infarction and its Regulation on Platelet Function, Current Neurovascular Research 2015; 12 (1) . https://dx.doi.org/10.2174/1567202612666150102125221