Impacts of COX-1 gene polymorphisms on vascular outcomes in patients with ischemic stroke and treated with aspirin

As the key point of function for aspirin to educe anti-platelet effects, cyclooxygenase-1 (COX-1) gene polymorphisms have long been suspected as a potential cause for aspirin nonresponsiveness. But this hypothesis has not been confirmed by large longitudinal studies. This study prospectively evaluated the impacts of COX-1 gene polymorphisms on stroke recurrence and other vascular events in a large cohort of Chinese patients with ischemic stroke and treated with aspirin. Between December 2009 and October 2012, consecutive patients with ischemic stroke and treated with aspirin were enrolled. Polymorphisms of four alleles (rs1330344, rs10306114, rs3842788 and rs5788) in COX-1 gene were determined at baseline. The primary endpoint was a composite of nonfatal ischemic stroke, myocardial infarction, and death from cardiovascular causes. Impacts of COX-1 gene polymorphisms on vascular outcomes were evaluated with multivariate analysis. A total of 859 patients were included in data analysis. The minor allele frequencies of rs1330344, rs10306114, rs3842788 and rs5788 were 38.53%, 0.12%, 6.64% and 5.53%, respectively. During 14.64 ± 7.44 months of follow-up, primary endpoint was observed in 67 (7.80%) patients. Incidence of primary endpoint was higher in patients with CC genotype of rs1330344 than in patients with CT or TT genotype (HR = 1.916, 95% CI: 1.126-3.260, P = 0.016). After being adjusted for potential confounding factors, rs1330344 CC genotype was still independently associated with incidence of primary endpoint (HR = 1.958, 95% CI: 1.151-3.332, P = 0.013). The impacts of other three tested polymorphisms on primary endpoint were unremarkable. In conclusion, in Chinese patients with ischemic stroke and treated with aspirin, CC genotype of rs1330344 may increase the risk of subsequent vascular events.