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Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort

Stroke is the second leading cause of death in the world. Approximately 80% of strokes are ischemic in origin. Many risk factors have been linked to stroke, including an increased level of plasminogen activator inhibitor-1 (PAI-1). PAI-1 levels increase and remain elevated in blood during the acute...

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Autores principales: Choi, Gun Ho, Cho, Sung Hwan, An, Hui Jeong, Park, Han Sung, Lee, Jeong Yong, Ko, Eun Ju, Oh, Seung Hun, Kim, Ok Joon, Kim, Nam Keun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178745/
https://www.ncbi.nlm.nih.gov/pubmed/37175749
http://dx.doi.org/10.3390/ijms24098041
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author Choi, Gun Ho
Cho, Sung Hwan
An, Hui Jeong
Park, Han Sung
Lee, Jeong Yong
Ko, Eun Ju
Oh, Seung Hun
Kim, Ok Joon
Kim, Nam Keun
author_facet Choi, Gun Ho
Cho, Sung Hwan
An, Hui Jeong
Park, Han Sung
Lee, Jeong Yong
Ko, Eun Ju
Oh, Seung Hun
Kim, Ok Joon
Kim, Nam Keun
author_sort Choi, Gun Ho
collection PubMed
description Stroke is the second leading cause of death in the world. Approximately 80% of strokes are ischemic in origin. Many risk factors have been linked to stroke, including an increased level of plasminogen activator inhibitor-1 (PAI-1). PAI-1 levels increase and remain elevated in blood during the acute phase of ischemic stroke, which can impair fibrinolytic activity, leading to coronary artery disease and arterial thrombotic disorders. Here, we present a case-control study of 574 stroke patients and 425 controls seen for routine health examination or treatment for nonspecific dizziness, nonorganic headache, or anxiety for positive family history of stroke at the Bundang Medical Center in South Korea. Polymorphisms in PAI-1 were identified by polymerase chain reaction/restriction fragment length polymorphism analysis using genomic DNA. Specifically, three variations (−675 4G>5G, 10692T>C, and 12068G>A) were linked to a higher overall prevalence of stroke as well as a higher prevalence of certain stroke subtypes. Haplotype analyses also revealed combinations of these variations (−844G>A, −675 4G>5G, 43G>A, 9785A>G, 10692T>C, 11053T>G, and 12068G>A) that were significantly associated with a higher prevalence of ischemic stroke. To the best of our knowledge, this is the first strong evidence that polymorphic sites in PAI-1 promoter and 3′-UTR regions are associated with higher ischemic stroke risk. Furthermore, the PAI-1 genotypes and haplotypes identified here have potential as clinical biomarkers of ischemic stroke and could improve the prognosis and future management of stroke patients.
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spelling pubmed-101787452023-05-13 Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort Choi, Gun Ho Cho, Sung Hwan An, Hui Jeong Park, Han Sung Lee, Jeong Yong Ko, Eun Ju Oh, Seung Hun Kim, Ok Joon Kim, Nam Keun Int J Mol Sci Article Stroke is the second leading cause of death in the world. Approximately 80% of strokes are ischemic in origin. Many risk factors have been linked to stroke, including an increased level of plasminogen activator inhibitor-1 (PAI-1). PAI-1 levels increase and remain elevated in blood during the acute phase of ischemic stroke, which can impair fibrinolytic activity, leading to coronary artery disease and arterial thrombotic disorders. Here, we present a case-control study of 574 stroke patients and 425 controls seen for routine health examination or treatment for nonspecific dizziness, nonorganic headache, or anxiety for positive family history of stroke at the Bundang Medical Center in South Korea. Polymorphisms in PAI-1 were identified by polymerase chain reaction/restriction fragment length polymorphism analysis using genomic DNA. Specifically, three variations (−675 4G>5G, 10692T>C, and 12068G>A) were linked to a higher overall prevalence of stroke as well as a higher prevalence of certain stroke subtypes. Haplotype analyses also revealed combinations of these variations (−844G>A, −675 4G>5G, 43G>A, 9785A>G, 10692T>C, 11053T>G, and 12068G>A) that were significantly associated with a higher prevalence of ischemic stroke. To the best of our knowledge, this is the first strong evidence that polymorphic sites in PAI-1 promoter and 3′-UTR regions are associated with higher ischemic stroke risk. Furthermore, the PAI-1 genotypes and haplotypes identified here have potential as clinical biomarkers of ischemic stroke and could improve the prognosis and future management of stroke patients. MDPI 2023-04-28 /pmc/articles/PMC10178745/ /pubmed/37175749 http://dx.doi.org/10.3390/ijms24098041 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Choi, Gun Ho
Cho, Sung Hwan
An, Hui Jeong
Park, Han Sung
Lee, Jeong Yong
Ko, Eun Ju
Oh, Seung Hun
Kim, Ok Joon
Kim, Nam Keun
Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort
title Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort
title_full Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort
title_fullStr Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort
title_full_unstemmed Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort
title_short Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort
title_sort association between pai-1 polymorphisms and ischemic stroke in a south korean case-control cohort
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178745/
https://www.ncbi.nlm.nih.gov/pubmed/37175749
http://dx.doi.org/10.3390/ijms24098041
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