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 Ecadherin 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.

Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma

“…TH2 inflammation appears to be a potent modulator of epithelial permeability, not only in the gut, but also the skin, nasal epithelium, and 16HBE cells (9, 11, 12). In the context of asthma, previous studies have reported decreased expression levels of certain junctional proteins, including epithelial cadherin, occludin and ZO-1 (8, 34–36). Prior work has also shown that innate immune mediators such as TNF-alpha can influence claudin expression in airway epithelial cells (18).…”

Nucleotide variants of the cancer predisposing gene CDH1 and the risk of non-syndromic cleft lip with or without cleft palate

“…The CDH1 rs16958383 has been found to have a borderline association with breast cancer in premenopausal, but not postmenopausal, women [25]. Recently, Ierodiakonou et al [26] showed that rs7186053, rs4783573 and rs16958383 may contribute to airway remodeling and lung function in asthma patients using inhaled corticosteroids, however their impact on pulmonary cancer has yet to be elucidated.…”

Near Fatal Asthma: Clinical and Airway Biopsy Characteristics

“…This study could not address the issue of the effect of CS on remodeling in NFE biopsied group. Other studies have yielded contradictory results [18, 19]. Thermoplasty and novel targeted therapies may prove much more beneficial against remodeling [20, 21].…”