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Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: Replicated findings in two nested case-control studies based on independent cohorts
Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden, Department of Medicine, University Hospital, SE-901 85 Umeå, Sweden.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
Department of Medical Clinical Genetics, Umeå University, Sweden.
Atherosclerosis Research Unit, King Gustav V Research Institute, Karolinska Hospital, Stockholm, Sweden.
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2005 (English)In: Stroke, ISSN 0039-2499, Vol. 36, no 8, 1661-1665 p.Article in journal (Refereed) Published
Abstract [en]

Background and Purpose - Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. Methods - A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. Results - The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87, 95% CI, 1.12 to 3.15 in study A, OR of 4G homozygosity, 1.56, 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. Conclusions - Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction. © 2005 American Heart Association. Inc.

Place, publisher, year, edition, pages
2005. Vol. 36, no 8, 1661-1665 p.
Keyword [en]
Genetics, Plasminogen activator inhibitor-1, Polymorphism, Stroke
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-50277DOI: 10.1161/01.STR.0000174485.10277.24OAI: diva2:271173
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2011-01-12

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