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PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immuno...

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Autores principales: Jiang, Shaowei, Wang, Yang, Chen, Liang, Mu, Honghua, Meaney, Connor, Fan, Yiwen, Pillay, Janesh, Wang, Hairong, Zhang, Jincheng, Pan, Shuming, Gao, Chengjin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431590/
https://www.ncbi.nlm.nih.gov/pubmed/37439338
http://dx.doi.org/10.1097/CM9.0000000000002316
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author Jiang, Shaowei
Wang, Yang
Chen, Liang
Mu, Honghua
Meaney, Connor
Fan, Yiwen
Pillay, Janesh
Wang, Hairong
Zhang, Jincheng
Pan, Shuming
Gao, Chengjin
author_facet Jiang, Shaowei
Wang, Yang
Chen, Liang
Mu, Honghua
Meaney, Connor
Fan, Yiwen
Pillay, Janesh
Wang, Hairong
Zhang, Jincheng
Pan, Shuming
Gao, Chengjin
author_sort Jiang, Shaowei
collection PubMed
description BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. METHODS: A total of 181 patients aged 18–80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. RESULTS: The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. CONCLUSIONS: Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.
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spelling pubmed-104315902023-08-20 PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity Jiang, Shaowei Wang, Yang Chen, Liang Mu, Honghua Meaney, Connor Fan, Yiwen Pillay, Janesh Wang, Hairong Zhang, Jincheng Pan, Shuming Gao, Chengjin Chin Med J (Engl) Original Article BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. METHODS: A total of 181 patients aged 18–80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. RESULTS: The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. CONCLUSIONS: Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity. Lippincott Williams & Wilkins 2023-07-13 2023-08-20 /pmc/articles/PMC10431590/ /pubmed/37439338 http://dx.doi.org/10.1097/CM9.0000000000002316 Text en Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Article
Jiang, Shaowei
Wang, Yang
Chen, Liang
Mu, Honghua
Meaney, Connor
Fan, Yiwen
Pillay, Janesh
Wang, Hairong
Zhang, Jincheng
Pan, Shuming
Gao, Chengjin
PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity
title PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity
title_full PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity
title_fullStr PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity
title_full_unstemmed PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity
title_short PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity
title_sort pai-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431590/
https://www.ncbi.nlm.nih.gov/pubmed/37439338
http://dx.doi.org/10.1097/CM9.0000000000002316
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