Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke
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...
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Ovid Technologies (Wolters Kluwer Health)
2005
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Online Access: | http://dx.doi.org/10.1161/01.str.0000174485.10277.24 https://www.ahajournals.org/doi/full/10.1161/01.STR.0000174485.10277.24 |
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crovidcr:10.1161/01.str.0000174485.10277.24 2024-10-13T14:09:50+00:00 Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke Replicated Findings in Two Nested Case–Control Studies Based on Independent Cohorts Wiklund, Per-Gunnar Nilsson, Lennart Ardnor, Sofie Nilsson Eriksson, Per Johansson, Lars Stegmayr, Birgitta Hamsten, Anders Holmberg, Dan Asplund, Kjell 2005 http://dx.doi.org/10.1161/01.str.0000174485.10277.24 https://www.ahajournals.org/doi/full/10.1161/01.STR.0000174485.10277.24 en eng Ovid Technologies (Wolters Kluwer Health) Stroke volume 36, issue 8, page 1661-1665 ISSN 0039-2499 1524-4628 journal-article 2005 crovidcr https://doi.org/10.1161/01.str.0000174485.10277.24 2024-09-17T04:25:18Z 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. Article in Journal/Newspaper Northern Sweden Ovid Stroke 36 8 1661 1665 |
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English |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Wiklund, Per-Gunnar Nilsson, Lennart Ardnor, Sofie Nilsson Eriksson, Per Johansson, Lars Stegmayr, Birgitta Hamsten, Anders Holmberg, Dan Asplund, Kjell |
spellingShingle |
Wiklund, Per-Gunnar Nilsson, Lennart Ardnor, Sofie Nilsson Eriksson, Per Johansson, Lars Stegmayr, Birgitta Hamsten, Anders Holmberg, Dan Asplund, Kjell Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke |
author_facet |
Wiklund, Per-Gunnar Nilsson, Lennart Ardnor, Sofie Nilsson Eriksson, Per Johansson, Lars Stegmayr, Birgitta Hamsten, Anders Holmberg, Dan Asplund, Kjell |
author_sort |
Wiklund, Per-Gunnar |
title |
Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke |
title_short |
Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke |
title_full |
Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke |
title_fullStr |
Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke |
title_full_unstemmed |
Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke |
title_sort |
plasminogen activator inhibitor-1 4g/5g polymorphism and risk of stroke |
publisher |
Ovid Technologies (Wolters Kluwer Health) |
publishDate |
2005 |
url |
http://dx.doi.org/10.1161/01.str.0000174485.10277.24 https://www.ahajournals.org/doi/full/10.1161/01.STR.0000174485.10277.24 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_source |
Stroke volume 36, issue 8, page 1661-1665 ISSN 0039-2499 1524-4628 |
op_doi |
https://doi.org/10.1161/01.str.0000174485.10277.24 |
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Stroke |
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36 |
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8 |
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1661 |
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1665 |
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1812816888029249536 |