SERPINE1-675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response

A. Dijkstra; D. S. Postma; M. Bruinenberg; C. C. van Diemen; H. M. Boezen; G. H. Koppelman; W. Timens; J. M. Vonk

doi:10.1183/09031936.00182410

SERPINE1-675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response

A. Dijkstra, D. S. Postma, M. Bruinenberg, C. C. van Diemen, H. M. Boezen, G. H. Koppelman, W. Timens, J. M. Vonk^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

22 Citations (Scopus)

Abstract

Asthma is characterised by chronic airway inflammation and remodelling, which can be (partially) suppressed by inhaled corticosteroids (ICSs). Plasminogen activator inhibitor-1, encoded by the SERPINE1 gene, is the key inhibitor of the plasminogen activator system, which affects tissue repair and remodelling.

We studied associations between a functional SERPINE1 -675 4G/5G promoter polymorphism and asthma development, severity and response to ICSs.

Longitudinal cohorts of 281 asthmatics and their nonasthmatic spouses, and the general population (n=1,390) were studied. No significant associations were found with asthma development and immunoglobulin (Ig) E levels, or with forced expiratory volume in 1 s (FEV(1)) in nonasthmatic controls. Asthmatic subjects carrying the SERPINE1 5G allele had higher IgE and lower lung function levels at follow-up, lower maximally attained lung function levels, and faster lung function decline compared with individuals with the 4G/4G genotype. ICS treatment showed an immediate improvement in FEV(1) in asthmatics carrying the 5G allele. However, these asthmatics still had the fastest rate of FEV(1) decline after initiating ICS treatment. Finally, the 5G allele was associated with a lower prevalence of complete asthma remission at follow-up.

These findings suggest that SERPINE1 is not an asthma susceptibility gene, but rather affects the severity, progression and long-term ICS response in asthma.

Original language	English
Pages (from-to)	1036-1043
Number of pages	8
Journal	European Respiratory Journal
Volume	38
Issue number	5
DOIs	https://doi.org/10.1183/09031936.00182410
Publication status	Published - Nov-2011

Keywords

Asthma remission
asthma severity
genetic
inhaled corticosteroids
lung function decline
plasminogen activator inhibitor-1
PLASMINOGEN-ACTIVATOR INHIBITOR-1
LUNG-FUNCTION DECLINE
INDUCED PULMONARY-FIBROSIS
30-YEAR FOLLOW-UP
PAI-1 GENE
RISK-FACTORS
MAST-CELLS
AIRWAY RESPONSIVENESS
PROMOTER POLYMORPHISM
RESPIRATORY SYMPTOMS

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@article{cf49df0984df4c7bb62a26002cb8f8f0,

title = "SERPINE1-675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response",

abstract = "Asthma is characterised by chronic airway inflammation and remodelling, which can be (partially) suppressed by inhaled corticosteroids (ICSs). Plasminogen activator inhibitor-1, encoded by the SERPINE1 gene, is the key inhibitor of the plasminogen activator system, which affects tissue repair and remodelling.We studied associations between a functional SERPINE1 -675 4G/5G promoter polymorphism and asthma development, severity and response to ICSs.Longitudinal cohorts of 281 asthmatics and their nonasthmatic spouses, and the general population (n=1,390) were studied. No significant associations were found with asthma development and immunoglobulin (Ig) E levels, or with forced expiratory volume in 1 s (FEV(1)) in nonasthmatic controls. Asthmatic subjects carrying the SERPINE1 5G allele had higher IgE and lower lung function levels at follow-up, lower maximally attained lung function levels, and faster lung function decline compared with individuals with the 4G/4G genotype. ICS treatment showed an immediate improvement in FEV(1) in asthmatics carrying the 5G allele. However, these asthmatics still had the fastest rate of FEV(1) decline after initiating ICS treatment. Finally, the 5G allele was associated with a lower prevalence of complete asthma remission at follow-up.These findings suggest that SERPINE1 is not an asthma susceptibility gene, but rather affects the severity, progression and long-term ICS response in asthma.",

keywords = "Asthma remission, asthma severity, genetic, inhaled corticosteroids, lung function decline, plasminogen activator inhibitor-1, PLASMINOGEN-ACTIVATOR INHIBITOR-1, LUNG-FUNCTION DECLINE, INDUCED PULMONARY-FIBROSIS, 30-YEAR FOLLOW-UP, PAI-1 GENE, RISK-FACTORS, MAST-CELLS, AIRWAY RESPONSIVENESS, PROMOTER POLYMORPHISM, RESPIRATORY SYMPTOMS",

author = "A. Dijkstra and Postma, {D. S.} and M. Bruinenberg and {van Diemen}, {C. C.} and Boezen, {H. M.} and Koppelman, {G. H.} and W. Timens and Vonk, {J. M.}",

year = "2011",

month = nov,

doi = "10.1183/09031936.00182410",

language = "English",

volume = "38",

pages = "1036--1043",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "EUROPEAN RESPIRATORY SOC JOURNALS LTD",

number = "5",

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TY - JOUR

T1 - SERPINE1-675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response

AU - Dijkstra, A.

AU - Postma, D. S.

AU - Bruinenberg, M.

AU - van Diemen, C. C.

AU - Boezen, H. M.

AU - Koppelman, G. H.

AU - Timens, W.

AU - Vonk, J. M.

PY - 2011/11

Y1 - 2011/11

N2 - Asthma is characterised by chronic airway inflammation and remodelling, which can be (partially) suppressed by inhaled corticosteroids (ICSs). Plasminogen activator inhibitor-1, encoded by the SERPINE1 gene, is the key inhibitor of the plasminogen activator system, which affects tissue repair and remodelling.We studied associations between a functional SERPINE1 -675 4G/5G promoter polymorphism and asthma development, severity and response to ICSs.Longitudinal cohorts of 281 asthmatics and their nonasthmatic spouses, and the general population (n=1,390) were studied. No significant associations were found with asthma development and immunoglobulin (Ig) E levels, or with forced expiratory volume in 1 s (FEV(1)) in nonasthmatic controls. Asthmatic subjects carrying the SERPINE1 5G allele had higher IgE and lower lung function levels at follow-up, lower maximally attained lung function levels, and faster lung function decline compared with individuals with the 4G/4G genotype. ICS treatment showed an immediate improvement in FEV(1) in asthmatics carrying the 5G allele. However, these asthmatics still had the fastest rate of FEV(1) decline after initiating ICS treatment. Finally, the 5G allele was associated with a lower prevalence of complete asthma remission at follow-up.These findings suggest that SERPINE1 is not an asthma susceptibility gene, but rather affects the severity, progression and long-term ICS response in asthma.

AB - Asthma is characterised by chronic airway inflammation and remodelling, which can be (partially) suppressed by inhaled corticosteroids (ICSs). Plasminogen activator inhibitor-1, encoded by the SERPINE1 gene, is the key inhibitor of the plasminogen activator system, which affects tissue repair and remodelling.We studied associations between a functional SERPINE1 -675 4G/5G promoter polymorphism and asthma development, severity and response to ICSs.Longitudinal cohorts of 281 asthmatics and their nonasthmatic spouses, and the general population (n=1,390) were studied. No significant associations were found with asthma development and immunoglobulin (Ig) E levels, or with forced expiratory volume in 1 s (FEV(1)) in nonasthmatic controls. Asthmatic subjects carrying the SERPINE1 5G allele had higher IgE and lower lung function levels at follow-up, lower maximally attained lung function levels, and faster lung function decline compared with individuals with the 4G/4G genotype. ICS treatment showed an immediate improvement in FEV(1) in asthmatics carrying the 5G allele. However, these asthmatics still had the fastest rate of FEV(1) decline after initiating ICS treatment. Finally, the 5G allele was associated with a lower prevalence of complete asthma remission at follow-up.These findings suggest that SERPINE1 is not an asthma susceptibility gene, but rather affects the severity, progression and long-term ICS response in asthma.

KW - Asthma remission

KW - asthma severity

KW - genetic

KW - inhaled corticosteroids

KW - lung function decline

KW - plasminogen activator inhibitor-1

KW - PLASMINOGEN-ACTIVATOR INHIBITOR-1

KW - LUNG-FUNCTION DECLINE

KW - INDUCED PULMONARY-FIBROSIS

KW - 30-YEAR FOLLOW-UP

KW - PAI-1 GENE

KW - RISK-FACTORS

KW - MAST-CELLS

KW - AIRWAY RESPONSIVENESS

KW - PROMOTER POLYMORPHISM

KW - RESPIRATORY SYMPTOMS

U2 - 10.1183/09031936.00182410

DO - 10.1183/09031936.00182410

M3 - Article

C2 - 21478212

SN - 0903-1936

VL - 38

SP - 1036

EP - 1043

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 5

ER -

SERPINE1-675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response

Abstract

Keywords

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