title: Thromboxane A2 receptor polymorphism in association with cerebral infarction and its regulation on platelet function.
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.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Shao
authors.forename: Yi
authors.initials: Y
authors.lastname: Fu
authors.forename: Wanlin
authors.initials: W
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Shengdi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Room 211, Med-X Building, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China. wlxia@sjtu.edu.cn.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Xia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002544:Cerebral Infarction / Q000097:blood* / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D056726:Genetic Association Studies; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics*; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D005340:Fibrinogen; D002118:Calcium