PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity.
10.1097/CM9.0000000000002316
- Author:
Shaowei JIANG
1
;
Yang WANG
1
;
Liang CHEN
1
;
Honghua MU
2
;
Connor MEANEY
2
;
Yiwen FAN
3
;
Janesh PILLAY
4
;
Hairong WANG
1
;
Jincheng ZHANG
5
;
Shuming PAN
1
;
Chengjin GAO
1
Author Information
1. Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
2. Division of Rheumatology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
3. Department of Pathology Medicine Biology, University Medical Center Groningen, The Netherlands.
4. Department of Critical Care, University Medical Center Groningen, The Netherlands.
5. Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
- Publication Type:Journal Article
- MeSH:
Adolescent;
Adult;
Aged;
Aged, 80 and over;
Humans;
Middle Aged;
Young Adult;
Genotype;
Neutrophils;
Plasminogen Activator Inhibitor 1/genetics*;
Polymorphism, Single Nucleotide/genetics*;
Retrospective Studies;
Sepsis/genetics*
- From:
Chinese Medical Journal
2023;136(16):1959-1966
- CountryChina
- Language:English
-
Abstract:
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.
