Tissue plasminogen activator -7351C/T enhancer polymorphism is a risk factor for lacunar stroke

Jim Jannes, Monica A. Hamilton-Bruce, Louis Pilotto, Brian J. Smith, Charles G. Mullighan, Peter G. Bardy, Simon A. Koblar

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53 Citations (Scopus)

Abstract

Background and Purpose - Occlusive thrombosis is an important component of small- and large-vessel ischemic stroke. Endogenous tissue plasminogen activator (TPA) is the primary mediator of intravascular fibrinolysis and is predominantly expressed by the endothelium of small vessels. The acute release of TPA is influenced by the TPA -7351C/T polymorphism and therefore may play an important role in the pathogenesis of lacunar stroke. In this study, we investigated the risk of lacunar and nonlacunar ischemic stroke associated with the TPA -735ICT polymorphism. Methods - We conducted a case-control study of 182 cases of ischemic stroke and 301 community controls. Participants were evaluated for known cerebrovascular risk factors, and the TPA -7351C/T genotype was established by a polymerase chain reaction (PCR) method. Logistic regression was used to determine the risk of lacunar and nonlacunar ischemic stroke associated with the TPA -7351C/T polymorphism. Results - The prevalence of the TPA -7351 CC, CT, and TT genotypes were 46%, 45%, and 9% for controls and 41%, 46%, and 13% for stroke patients, respectively. After adjustment for known cerebrovascular risk factors, the TT genotype was significantly associated with ischemie stroke (OR: 1.9; 95% CI: 1.01 to 3.6). Stratification for stroke subtype showed a significant association between the TT genotype and lacunar stroke but not nonlacunar stroke (OR: 2.7; 95% CI: 1.1 to 6.7). Conclusions - The TPA -7351C/T polymorphism is an independent risk factor for lacunar stroke. The findings suggest that impaired fibrinolysis may play a role in the pathogenesis of lacunar stroke.

Original languageEnglish
Pages (from-to)1090-1094
Number of pages5
JournalStroke
Volume35
Issue number5
DOIs
Publication statusPublished or Issued - May 2004

Keywords

  • Genetics
  • Lacunar infarction
  • Polymorphism
  • Tissue plasminogen activator

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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