title: Impacts of COX-1 gene polymorphisms on vascular outcomes in patients with ischemic stroke and treated with aspirin.
abstract: 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.
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China; Department of Neurology, Nanjing Jiangning Hospital, Nanjing 210002, China.
authors.forename: Wenshan
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Bai
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Biyang
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Zuowei
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Qiankun
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, China. Electronic address: gelinxu@gmail.com.
authors.forename: Gelin
authors.initials: G
authors.lastname: Xu
mesh_terms: D000368:Aged; D000483:Alleles; D001241:Aspirin / Q000008:administration & dosage*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D051545:Cyclooxygenase 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011110:Polymorphism, Genetic; D020521:Stroke / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics
chemical_list: D010975:Platelet Aggregation Inhibitors; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin
keywords: Aspirin nonresponsiveness; Prospective cohort study; Single nucleotide polymorphism