The Clinical Factors Of Aspirin Resisitance And The Association Of The Cyclooxygenase-2 Gene Polymorphism With Aspirin Resistance

Objective The study was designed to investigate the clinical factors of aspirin resistance and to measure -765C>G subsititution in the promoter region of COX-2 gene and the association of the cox-2 gene -765C>G polymorphism with aspirin resistance.Methods (1)424 patients with cardiovascular diseases who had taken aspirin were detected platelet aggregation indued by arachidonic acid and adenosine diphosphate.They were devided into aspirin resistance(AR) group or semiresistance (ASR) group and asipirin sensitive(AS) group. (2) To count the gender and the age of all patients and the number of the patients with diabetes,hypertension,metabolic syndrome and renal disfunction. Plasma TC, TG ,LDL ,HDL and fibrinogen were test in some subjects. And the relationship between these clinical factors and aspirin resistance was investigated. (3)105 and 117 patients were selected from aspirin resistance or semiresistance group and aspirin sensitive group respectively to determine cox-2 -765C/G polymorphism .Genomic DNA was extracted from AR or ASR and AS group,306 bp DNA fragment of cox-2 promoter region was amplified by polymerase chain reaction (PCR).The -765C/G polymorphism was genotyped by AciI restriction endonuclease digest PCR product and eletrophoresis by agarose gel el.The association of cox-2 gene -765C/G polymorphism with aspirin resistance were investigated. (4) 5 patients with aspirin resistance or semiresistance were treated by cardiotonic pill instead of aspirin and 43 patients with aspirin resistance or remiresistance were treated by aspirin and cardiotonic pill ,the clinic effects were investigated.Results (1) 4.24% of the patients were aspirin resistance and 20.99% were aspirin semiresistance. (2) The clinical characteristics of AR or ASR compared with AS patients included: female(61/107 vs 141/317,p<0.05);patients with hypertensio(40/107 vs 76/317,p<0.05);patients with diabetes (41/107 vs 51/317,p<0.05);patients with metabolic syndrome( 12/78 vs 16/229,p<0.05);patients with renal disfunction (7/78 vsl8/231,p<0.05), plasma LDL (3.1477 + 0.8041 mmol/L vs 2.8552 + 0.7575 mmol/L ,p<0.05) .The age and plasma TC, TG, HDL, Fg showed no significant difference between two group. The logistic analysis showed that diabetes,hypertension and high plasma LDL were the risk factors of AR or ASR.(3) The frequency of -765G/C genotype was 16.82%(AR or ASR group)and 9.40% (AS group), (p=0.111) , the frequency of G allele was 8.57%(AR or ASR group) and 4.70%( AS group) , (p=0.124) .There was no significant difference for both G/C genotype and G allele between two groups. (4) 43 patients of AR or ASR group were treated by aspirin and carditonic pill,the platelet aggregation(%) was decreased from 65.39+23.61 to 35.23+24. 59(AA indued,p<0.05) and from 45.12 + 24. 55 to 29.91 +16.15(ADP indued,p<0.05).25patients from AR or ASR group became to AS.Conclusion (1) The incidence of aspirin resistance is similar to the other studies published before.(2) Female, diabetes,hypertension ,metabolic syndrome and high LDL level are risk factors of aspirin resistance.(3) Although the polymorphism ofcox-2 gene -765c did not play an important and direct role in the pathogenesis of aspirin resistance, it might have indirect effect on it. (4) Cardiotonic pill is benefit to the patients with aspirin resistance or semiresistance..