E-cadherin gene polymorphisms in asthma patients using inhaled corticosteroids

Abstract

E-cadherins form intercellular junctions that maintain epithelial integrity. Epithelial integrity is impaired in asthma and can be restored by inhaled corticosteroids (ICSs). Our aim was to investigate the association of CDH1 gene polymorphisms (single-nucleotide polymorphisms (SNPs)) with airway remodelling, inflammation and forced expiratory volume in 1 s (FEV₁) decline in asthma patients and assess whether ICSs modulate these effects. Bronchial biopsies of 138 asthmatics were available (population 1). Associations of 17 haplotype-tagging SNPs with epithelial E-cadherin expression, biopsy parameters and FEV₁/vital capacity (VC) ratio were tested. FEV₁ and VC data were collected in 281 asthmatics with 30-yr follow-up (population 2). Linear mixed-effect models were used to assess associations of SNPs with FEV₁ decline. Seven out of the 17 SNPs were associated with airway remodelling, three with CD8+ T-cell counts, two with eosinophil counts and seven with FEV₁ decline. All associations occurred only in patients using ICS. In general, alleles associated with less remodelling correlated with less FEV₁ decline and higher FEV₁/VC. Decreased epithelial E-cadherin expression was associated with five SNPs in non-ICS users. In conclusion, our data show that CDH1 polymorphisms are associated with epithelial E-cadherin expression and suggest that epithelial adhesion is an important contributor to airway remodelling and lung function in asthma. These effects are modified by the use of inhaled corticosteroids.