Impact of COX-2 rs5275 and rs20417 and GPIIIa rs5918 Polymorphisms on 90-Day Ischemic Stroke Functional Outcome: A Novel Finding

• Published in: Journal of stroke and cerebrovascular diseases 2011-03, Vol.20 (2), p.134-144
• Main Authors: Maguire, Jane, BA, BNurs(Hons), Thakkinstian, Ammarin, PhD, Levi, Christopher, MBBS, Lincz, Lisa, PhD, Bisset, Linda, Masters, Sturm, Jonathan, PhD, Scott, Rodney, PhD, Whyte, Scott, PhD, Attia, John, PhD
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Brain Ischemia - complications; Brain Ischemia - diagnosis; Brain Ischemia - enzymology; Brain Ischemia - genetics; Brain Ischemia - physiopathology; Cardiovascular; Case-Control Studies; Chi-Square Distribution; Cyclooxygenase 2 - genetics; Disability Evaluation; Female; functional recovery; Gene Frequency; Genetic Predisposition to Disease; Genetics; Hospitals, Public; Humans; Integrin beta3 - genetics; Logistic Models; Male; Middle Aged; Neurology; New South Wales; Odds Ratio; Phenotype; Plasminogen Activator Inhibitor 1 - genetics; Polymorphism, Genetic; post stroke; Recovery of Function; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke - diagnosis; Stroke - enzymology; Stroke - genetics; Stroke - physiopathology; Time Factors; Tissue Plasminogen Activator - genetics
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2009.10.011

We hypothesized that polymorphisms in 5 genes related to thrombolytic and inflammation pathways will independently influence occurrence, severity, and 3-month functional outcome in patients with ischemic stroke. This was a case-control design with ischemic stroke patients recruited from 4 public hospitals (n = 640) and community controls (n = 627). Baseline clinical data were collected, and follow-up telephone interviews were conducted with 520 patients at 90 days postevent to determine stroke outcome using the Barthel Index (BI), Modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS). Blood samples were collected and genotyped for polymorphisms in platelet glycoprotein Ibα (GPIbα) rs224309 and rs6065, glycoprotein IIIa (GPIIIa) rs5918, tissue plasminogen activator (tPA) rs63020761, plasminogen activating inhibitor (PAI-1) rs72578597, and cyclooxygenase-2 (COX-2) rs5275 and rs20417. COX-2 polymorphism rs5275 demonstrated a significant association with poststroke mRS, with a dominant genetic model demonstrating the best fit (CC + TC) (adjusted odds ratio [aOR] = 1.61; P = .026). The COX-2 rs20417 C allele showed an association with GOS (aOR = 1.95; P = .012), and again a dominant genetic model demonstrated the best fit (CC + GC). GPIIIa rs5918 (A1A2) was associated with poststroke BI, with a dominant model demonstrating the best fit (A1A2 + A2A2) (aOR = 0.56; P = .014). There was a significant association between stroke severity and tPA rs63020761 TT allele (aOR = 1.96; 95% CI = 1.03-3.72; P = .040). This is the first study to demonstrate associations between stroke functional outcome and 2 COX-2 variants (rs20417 and rs5275) and a GPIIIa variant (rs5918).