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

• Published in: The European respiratory journal Vol. 38; no. 5; pp. 1036 - 1043
• Main Authors: Dijkstra, A., Postma, D.S., Bruinenberg, M., van Diemen, C.C., Boezen, H.M., Koppelman, G.H., Timens, W., Vonk, J.M.
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.11.2011
• Subjects: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents - administration & dosage; Asthma - drug therapy; Asthma - genetics; Asthma - immunology; Asthma - physiopathology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chronic obstructive pulmonary disease, asthma; Female; Forced Expiratory Volume; Glucocorticoids - administration & dosage; Humans; Immunoglobulin E - blood; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Plasminogen Activator Inhibitor 1 - genetics; Pneumology; Polymorphism, Genetic; Remission Induction; Respiratory Function Tests; genetic; Lung disease; Corticosteroid; Respiratory disease; Asthma remission; lung function decline; asthma severity; Asthma; Inhalation; Lung function; plasminogen activator inhibitor-1; Activator; Bronchus disease; Genetics; Remission; Inhibitor; Obstructive pulmonary disease; Plasminogen; Pneumology; Polymorphism; inhaled corticosteroids
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/09031936.00182410

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.