Platelet Response to Aspirin in Chinese Stroke Patients is Independent of Genetic Polymorphisms of COX-1 C50T and COX-2 G765C

Abstract

Aim: Aspirin resistance (AR) is common in Chinese stroke patients taking antiplatelet medications; however, few studies have documented the role of cyclooxygenase (COX)-1 C50T and COX-2 G765C polymorphisms in AR. The aim of this study was to investigate the prevalence of AR in Chinese stroke patients and the relationships between AR and COX-1 C50T and COX-2 G765C polymorphisms, and to evaluate the effect of these polymorphisms on platelet response to aspirin. Methods: We prospectively enrolled 634 Chinese stroke patients. Platelet aggregation testing was performed before and after aspirin administration. The pre-and post-aspirin levels of 11-dehydrothromboxane B2 (11-dTxB2) were determined in urine samples. COX-1 C50T and COX-2 G765C genotypes were determined by a polymerase chain reaction-allelic restriction assay. Results: AR was detected in 129 patients (20.4%), aspirin semi-resistance (ASR) was detected in 28 patients (4.4%), and aspirin sensitivity (AS) was detected in 477 patients (75.2%). There was no association between COX-1 C50T or COX-2 G765C polymorphisms and ASR＋AR. Aspirin could efficiently reduce 11-dTxB2 production by approximately 75%. In addition, platelet aggregation, both in response to arachidonic acid (AA) and adenosine 5'-diphosphate (ADP), was inhibited by more than 80% and 40%, respectively; however, the percentage reduction in platelet aggregation and 11-dTxB2 levels was not significantly different between the COX-1 C50T and COX-2 G765C genotypes (p＞0.05). Conclusions: There was no association between COX-1 C50T and COX-2 G765C polymorphisms and AR in Chinese stroke patients. In addition, COX-1 C50T and COX-2 G765C polymorphisms had no effect on the platelet response to aspirin. J Atheroscler Thromb, 2013; 20:65-72.

Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients

“…We found that the prevalence of AR and ASR was 20.6 and 5.3%, respectively, and that diabetes mellitus was associated with AR. These findings were in accordance with previous studies [5, 18, 27]. Further, aside from variant P2Y1 (rs1371097), we found no significant differences in the distribution of the other variants between the AR + ASR group and AS group.…”

“…Polymorphisms in COX -2 rs20417 and COX-1 C50T have been reported to be associated with impaired aspirin responsiveness [13, 14]. However, in both a previous study [18] and this study, these polymorphisms were not found to be associated with AR in acute IS patients. P2Y12 and P2Y1 are platelet membrane receptors and play a key role in platelet aggregation, thrombosis and the pharmacology of antiplatelet therapy [9].…”

“…Platelet aggregation was measured by light transmittance aggregometry (LTA), as described previously [2, 5, 18]. A mean aggregation of ≥70% with 10 μM ADP and a mean aggregation of ≥20% with 0.5 mM AA after aspirin intake for 7 to 10 days were defined as AR.…”

“…A mean aggregation of ≥70% with 10 μM ADP or a mean aggregation of ≥20% with 0.5 mM AA was defined as Aspirin semi-resistance (ASR). Patients with AR and those with ASR were pooled into an AR + ASR group [5, 18]. Otherwise, patients were considered aspirin sensitive (AS).…”

“…For example, polymorphisms in COX-1, COX-2, GPIIIa, P2Y1 , P2Y12 were reported to contribute to AR [12–17]. However, other studies, including a previous study published by this group, did not find aspirin responsiveness to be associated with these variants in patients with symptomatic vascular disease [18–20]. Thus, the role of SNPs in COX-1, COX-2 , GPIb, GPIIIa, P2Y1, P2Y12 in AR remains controversial [21].…”