title: Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients.
abstract: BACKGROUND
  The effect of genetic variants on aspirin resistance (AR) remains controversial. We sought to assess the association of genetic variants with AR and early clinical outcomes in patients with acute ischemic stroke (IS).
  
  
  METHODS
  A total of 850 acute IS patients were consecutively enrolled. Platelet aggregation was measured before and after a 7-10 day aspirin treatment. The sequences of 14 variants of COX-1, COX-2, GPIb, GPIIIa, P2Y1 and P2Y12 were determined using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). The primary outcome was early neurological deterioration (END) within 10 days of admission. The secondary outcome was a composite of early recurrent ischemic stroke (ERIS), myocardial infarction (MI) and death within 10 days of admission.
  
  
  RESULTS
  175 (20.6%) patients were AR, 45 (5.3%) were aspirin semi-resistant, 121 (14.2%) developed END, 17 (0.2%) had ERIS, 2 (0.2%) died, and 6 (0.7%) had MI. Single locus analysis indicated that only rs1371097 was associated with AR. However, GMDR analysis indicated that the following three sets of gene-gene interactions were significantly associated with AR: rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097CT/rs2317676AG. END occurred significantly more frequently in patients with AR or high-risk interactive genotypes. Moreover, AR and high-risk interactive genotypes were independently associated with END.
  
  
  CONCLUSIONS
  Sensitivity of IS patients to aspirin and END may be multifactorial and is not significantly associated with a single gene polymorphism. Combinational analysis may useful for further insight into the genetic risks for AR.
authors.affiliation: Department of Neurology, People's Hospital of Deyang City, No 173, North Taishan Road, Deyang, 618000, Sichuan, China. 1842942576@qq.com.
authors.forename: Xingyang
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Neurology, People's Hospital of Deyang City, No 173, North Taishan Road, Deyang, 618000, Sichuan, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, No 108 Wanson road, Ruan City, Wenzhou, 325200, Zhejiang, China. zhouqiang5613@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, No 108 Wanson road, Ruan City, Wenzhou, 325200, Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D002681:China; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; D058472:Receptors, Purinergic P2Y1; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D001241:Aspirin
keywords: Aspirin resistance; Early neurological deterioration; Genetic variants; Ischemic stroke; Polymorphism