Variants in COX-2, PTGIS, and TBXAS1 Are Associated with Carotid Artery or Intracranial Arterial Stenosis and Neurologic Deterioration in Ischemic Stroke Patients

J Stroke Cerebrovasc Dis. 2017 May;26(5):1128-1135. doi: 10.1016/j.jstrokecerebrovasdis.2016.12.032. Epub 2017 Jan 17.

Abstract

Background: Eicosanoids may play a role in ischemic stroke (IS). However, the association of variants in eicosanoid genes with symptomatic carotid artery or intracranial arterial stenosis and neurologic deterioration (ND) is not fully understood. The aim of the present study was to investigate the association of 11 variants in eicosanoid genes with symptomatic carotid artery or intracranial arterial stenosis and ND.

Methods: Eleven variants in eicosanoid genes were examined using mass spectrometry method in 297 IS patients. The symptomatic carotid artery or intracranial arterial stenosis was assessed by computed tomographic angiography. Platelet aggregation and platelet-leukocyte aggregates were measured. The primary outcome was ND within 10 days of admission. ND was defined as an increase of 2 or more points in National Institutes of Health Stroke Scale score.

Results: Among 297 IS patients, 182 (61.3%) cases had symptomatic carotid artery or intracranial arterial stenosis, and 88 (29.6%) patients experienced ND within 10 days after admission. Symptomatic carotid artery or intracranial arterial stenosis was significantly associated with higher ND (P < .001). Rs20417CC, rs41708TT, and rs5629CC were independent risk factors for symptomatic carotid artery or intracranial arterial stenosis and ND, and associated with higher platelet aggregation and platelet-leukocyte aggregates.

Conclusions: Symptomatic carotid artery or intracranial arterial stenosis was associated with higher ND. Rs20417CC, rs41708TT, and rs5629CC were not only independent risk factors for symptomatic carotid artery or intracranial arterial stenosis, but also independent risk predictors for ND.

Keywords: Ischemic stroke; carotid stenosis; eicosanoic acids; intracranial arterial stenosis; neurological deterioration; single nucleotide polymorphisms.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain Ischemia / diagnosis
  • Brain Ischemia / enzymology
  • Brain Ischemia / genetics*
  • Brain Ischemia / physiopathology
  • Carotid Stenosis / diagnostic imaging
  • Carotid Stenosis / enzymology
  • Carotid Stenosis / genetics*
  • Carotid Stenosis / physiopathology
  • Cerebral Arterial Diseases / diagnostic imaging
  • Cerebral Arterial Diseases / enzymology
  • Cerebral Arterial Diseases / genetics*
  • Cerebral Arterial Diseases / physiopathology
  • China
  • Cyclooxygenase 2 / genetics*
  • Cytochrome P-450 Enzyme System / genetics*
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / enzymology
  • Stroke / genetics*
  • Stroke / physiopathology
  • Thromboxane-A Synthase / genetics*
  • Time Factors

Substances

  • Cytochrome P-450 Enzyme System
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • PTGIS protein, human
  • Thromboxane-A Synthase