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The Study Of COX-1,COX-2 Gene Polymorphisms With Aspirin Resistance In Ischemic Stroke Patients

Posted on:2017-10-14Degree:MasterType:Thesis
Country:ChinaCandidate:X LiFull Text:PDF
GTID:2334330485473822Subject:Neurology
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Part 1 Recurrence of ischemic stroke associated aspirin resistance and risk factors: Correlation Study.Objective: To investigate aspirin efficacy in ischemic cerebral infarction and recurrent patients,to discuss the relationship between recurrence of ischemic cerebral infarction and aspirin resistance.And then analysis the risk factors of recurrent ischemic cerebral infarction patients.Methods:By retrospective study,we enrolled 116 patients with acute,ischemic cerebral infarction from June 2014 and September 2015 hospitalized in the second hospital of He Bei medical university,which 81 cases in male,35 cases in female,their ages are from 31 to 82,the average age is(59.53±9.78). According to the number of clinical onset,all patients can be divided into primary and recurrent group,their are 42 cases(male 28,female 14) in primary group and 74 cases(male 53,female 21) in recurrent group.Recurrence group selected as the standard for the last 1 year after hospitalized in stable to continue use of aspirin 100mg/d.All cases were regular use of aspirin for more than 1 month,which recurrence patients on admission day through thromboelastography(TEG) to detect aspirin efficacy. The criteria of aspirin resistance is arachidonic acid(AA) induced platelet inhibition rate <50%.To compared the incidence of AR in two groups. Records of all patients admitted to hospital within 24 hours of three major routine,electrolyte,blood coagulation function,biochemical,homocysteine and other indicators.And compare clinical features in two groups like: age, sex, BMI, hypertension, DM, LAA, HDL-C, LDL-C, HCY, CRP, et al. The risk factors were analyzed by Logistic regression analysis, then discussed the correlation between risk factors and recurrent ischemic cerebral infarction.Results: TEG test results shows that: 42 patients in primary group, 12 cases of aspirin resistance, 30 cases of aspirin sensitive; In 74 patients with recurrence, 42 cases of aspirin resistance, 32 cases of aspirin sensitive, The incidence of AR(56.76%) in recurrence group were significantly higher than that in primary group(28.57%)(P< 0.01). Diabetes and coronary heart disease(CHD) in recurrence group were higher by statistically significant(P < 0.05). The risk factors of P<0.2 were selected by logistic regression analysis showed that recurrence were significantly correlated with aspirin resistance(AR)(OR 2.92, 95%CI : 1.255-6.794, P<0.05) and diabetes(OR 2.655, 95%CI :1.142-6.172,P<0.05). Part 2 Association study of COX-1?COX-2 gene polymorphism and aspirin resistance in ischemic stroke patientsObjective: To analyze the relationship between-1676A>G C50 T, A842 G, COX-2 and-G765 C COX-1 polymorphism and aspirin resistance in ischemic stroke.Methods: Selected 70 patients with first-ever acute ischemic stroke between October 2014 and June 2015 in the second hospital of Hebei Medical University.The COX-1 and COX-2 gene of four single nucleotide polymorphisms were examined by PCR and gene sequencing. Platelet inhibition were conducted for 70 patients when they were taking aspirin for 7 days by TEG, with AA induced aspirin inhibition rate of 50%,all patients were divided into aspirin resistance group(AR) and aspirin sensitive group(AS), to analysis the related gene polymorphism. The age, hypertension, DM, HDL, LDL, CHOL, TG, gender were compared, to discuss AR clinical related factors.All the patients were follow-up for 6 months, the primary endpoint was ischemic stroke recurrence. Impacts of COX-1,COX-2 gene polymorphisms on vascular outcomes were evaluated with x2 test.Results:1 According to TEG,45(64.3%)cases in AS group, 25(35.7%) cases in AR group.There were no significant differences of age, sex, BMI, hypertension, diabetes, CHOL, TG, LDL, HDL, HCY in two groups;2 There were no significant differences in the genotype distribution of COX-1 –A842G, C50 T,-1676A>G, COX-2-G765 C between AR and AS group;3During 6 months of follow-up, 12(17.14%) cases of adverse events,the primary endpoint was observed in 8(11.4%) patients. Secondary end points was observed in 4 patients(5.7%), including 2 cases of cerebral hemorrhage(2.9%), 1 cases of non fatal myocardial infarction(1.4%) and 1 cases of death(1.4%). Comparison of the primary endpoint between AS group and AR group showed that: The incidence of recurrent cerebral infarction was higher in AR group(P<0.05);4 Incidence of primary endpoint were no significant differences in patients with CC genotype of rs1330344 and GG genotype of rs20417 than in patients with CT or TT genotype of rs1330344 and GC or CC genotype of rs20417(P>0.05).Conclusion:1 Aspirin resistance and diabetes can significantly increase the risk of recurrent ischemic stroke;2 The COX1-A842 G and C50 T polymorphisms are rare in Chinese, which is not obviously associated with aspirin resistance.3 The impacts of COX-1-1676A>G and COX-2-G765 C polymorphisms on primary endpoint and treated with aspirin in Chinese patients were unremarkable.
Keywords/Search Tags:Aspirin resistance, Thrombelastogram, Ischemic cerebral infarction, COX-1 receptor, COX-2 receptor
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