The Contribution Of GPIa And COX-2 Gene Polymorphisms To Aspirin Resistance

Objective: Aspirin is commonly used in the treatment of acute ischemic stroke.In this study,to explore the association between GPIa,COX-2 gene polymorphisms and aspirin resistance in the south Han population of Jiangsu Province.The influencing factors of patients with aspirin resistance were investigated.Methods:97 patients with acute ischemic stroke were enrolled in the sudy, They were treated with aspirin 100 mg daily. Platelet aggregation induced with arachidonic acid(AA) and serum 11-DH-TXB2 were measured after these patients had been hospitalized and taken aspirin 100 mg for 7 days.Their GPIa gene polymorphism at 807C>T(rsl126643)and COX-2 gene polymorphism at-765G>C( rs20417) were genotyped by PCR-pyrosequencing technology.Patients were divided into the aspirin sensitivity(AS) group and aspirin resistance(AR) group with platelet max aggregationrate(MAR) induced by AA over 33.3% or not. The relationship between two gene polymorphisms and aspirin resistance were investigated.The age,gender,hypertension,diabetes, fasting plasma glucose, PLA2,CRP,blood lipids,PLT, RBC,and blood uric acid were compared between the AS and the AR groups. The NIHSS score,TOAST classification,OCSP classification were compared between two groups.Result:43 of 97 patients with acute ischemic stroke had the problem of AR.The clinical characteristics of participants,NIHSS score,TOAST classification and OCSP classification were similar between AS and AR groups. The serum 11-DH-TXB2 level was positively correlated with the maximum aggregation rate.The distribution frequencies of 807C>T genotypes(CC,CT,TT,CT+TT and CC) of GPIa and allele T were significantly different in AS and AR groups in female patients(P<0.05).Logistic regression analysis showed that the 807C>T CT+TT genotypes were significantly correlated with AR after adjustment for relative factors(P=0.047,OR=4.856,95%CI:1.020~23.108).There were no significant differences in the genotype distribution and allele frequency of COX-2 between two groups(p>0.05).Conclusion:We can use the platelet aggregation and the serum 11-DH-TXB2 levels to evaluate of aspirin resistance.GPIa gene polymorphism at 807C>T is associated with AR in Chinese Han females but not in males.No significant differences in the genotype distribution and allele frequency of COX-2 between AS and AR groups were found.