| Background: Cerebral infarction(CI) is a life-threatening disease resulting from a disturbance in the blood supply to the cerebral tissue, which has become one of the most serious public health problems characterized by high morbidity, disability and mortality rate. CI is a multifactorial disease influenced by genetic, environmental and vascular risk factors, but the specific pathogenetic mechanisms involved remain unclear. Thromboxane A2 receptor(TXA2R) is widely distributed in vivo, which can be specifically activated by Thromboxane A2(TXA2). It plays an important role in platelet activation, adhesion and aggregation. The single nucleotide polymorphisms(SNPs) of TXA2 R gene confer risks to CI, which might lead to the alterations of platelet function, thereby affect the pathological process of athersclerosis, finally influence thrombus formation.Methods:(1) Polymerase chain reaction and ligase detection reaction(PCR-LDR) was performed in 418 CI patients and 363 healthy individuals to examine four SNPs in human TXA2 R gene(C795T, T924 C and G1686 A in exon, and rs768963, rs2271875 in the promoter region). The distribution was assessed by SPSS 18.0.(2) The assessment of all patients was done at first day(admission day) based on the National Institutes of Health Stroke Severity Scale(NIHSS). CI patients were assessed poststroke disability one year after the acute event by the modified Rankin Scale(m RS).(3) The level of platelet aggregation rate, platelet-monocyte aggregations and cytoplasmic calcium was tested in all subjects, including CI patients and control group. TXA2 R antagonist SQ29548, Calcium channel blocker BAPTA and TXA2 R agonist U46619 were added in three tests respectively. Data were analysised by SPSS among three different genotypes on SNP rs768963.Results:(1) CI was significantly correlated with rs768963 genotype and allele in promoter region adjusted by tranditional risks(p=0.005, 0.001), CC genotype has a higher risk on CI(95% CI=1.082-3.049,p=0.024). CC+TC genotype confers a 3.361-fold high risk on CI than TT genotype group(95% CI=1.284-8.799,p=0.014)(2) GG+GA frequencies on rs2271875 of the good recovery group were higher than the TT genotype, conferring a lower risk on poor outcome(95% CI=0.262-0.919,p=0.026).(3) CC+TC genotype carriers had a higher platelet aggregation rate induced by Collagen than TT genotype carriers on SNP rs768963(p=0.007,p=0.01).The inhibition rate was the highest of TT genotype in 5min after SQ29548 added. The level of PMA of TT carriers was significant higher than CC carriers. BAPTA inhibit the PMA expression, while the reduction rate was the lowest of CC carriers compared to TT carriers(p=0.026). Cytoplasmic rest calcium shows no different among three genotypes, however, the constration of Ca2+ was significantly increased in TT carriers induced by U46619(p=0.007).Conclusion: TXA2 R gene rs768963 C allele might link to cerebral infarction and severity of neural function defect in Chinese population. rs2271875 GG genotype carriers were associated with a better outcome. C allele on rs768963 might be associated a higher platelet aggregation rate, PMA overexpression. Abnormal functional activation was detected in Platelet of CI patients with C allele, while SQ29548 and BAPTA could act as an effective antagonist. |
