Association Of The Platelet Membrane Glycoprotein Ⅰa C807T Gene Polymorphism With Aspirin Resistance

Section I Correlation of Aspirin Resistance and Serum Thromboxane B2Objective To explore the mechanisms of aspirin resistance in the patients with high-risk factors of atherosclerosis, and analyze its relationship with serum TXB2 level.Methods Two hundred patients took aspirin (100mg/d) for more than 7 days.We detected platelet aggregation function using 5μmol/L adenosine diphosphate (ADP) and 500μmol/L arachidonic acid (AA). We also measured serum TXB2 levels.Results 4.5% of the patients showed aspirin resistant (AR), 20.5% are aspirin semi-responders(ASR), and 75% are aspirin-sensitive(AS). Patients in AR or ASR group were more likely to be women or current smokers. Serum TXB2 levels of cases with high-risk of atherosclerosis were higher than that of control group (P<0.01). Serum TXB2 levels of cases who are AR or ASR were also significantly higher than that of aspirin-sensitive cases (P<0.01).Conclusion Serum TXB2 level has obvious relationship with the aspirin effect.Aspirin resistance may contribute to the occurrence of cardiovascular events in the patients with high-risk factors of atherosclerosis. SectionⅡAssociation of the Platelet Membrane GlycoproteinⅠa C807T Gene Polymorphism With Aspirin ResistanceBackground Aspirin antiplatelet effect is not uniform in all patients, and the mechanism by which some patients are resistant to aspirin remains to be determined. However, it has been suggested that polymorphisms of platelet membrane glycoproteinⅠa might contribute to aspirin resistance.Objective To explore the correlation between the C807T polymorphism of platelet membrane glycoproteinⅠa (GPⅠa)gene and aspirin resistance in Chinese people.Methods 200 patients with high-risk of atherosclerosis took aspirin(100mg/d) for 7 days. Platelet aggregation function was detected using 5μmol/L adenosine diphosphate (ADP) and 500μmol/L arachidonic acid (AA) before and after taking aspirin. Then they were divided into three groups according to the result of platelet aggregation function: aspirin resistant (AR) group, aspirin semi-responder (ASR) group and aspirin-sensitive(AS) group. Platelet GPⅠa gene 807C/T polymorphism was checked by means of polymerase chain reaction-sequence specific primers (PCR- SSP).Results T allelic frequency in AR group and ASR group were higher as compared to AS group (P<0.005), and the prevalence of genotypes (TT+TC) of these two groups were significantly higher than that in AS group (P<0.05). Platelet GPⅠa T allele was significantly associated with aspirin resistance by multiple logistic regression(OR=3.76, 95%CI: 2.87~9.58).Conclusion The results suggest that inherited platelet GPⅠa variations may have an important impact on aspirin resistance and the presence of GPⅠa T allele may be a marker of genetic susceptibility to aspirin resistance.