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E-cadherin gene polymorphisms in asthma patients using inhaled corticosteroids.

Authors: Ierodiakonou, D  Postma, DS  Koppelman, GH  Boezen, HM  Gerritsen, J  Ten Hacken, N  Timens, W  Vonk, JM 
Citation: Ierodiakonou D, etal., Eur Respir J. 2011 May 3.
Pubmed: (View Article at PubMed) PMID:21540309
DOI: Full-text: DOI:10.1183/09031936.00194710

E-cadherins form intercellular junctions that maintain epithelial integrity. Epithelial integrity is impaired in asthma and can be restored by inhaled corticosteroids (ICS). Our aim was to investigate the association of CDH1 gene polymorphisms (SNPs) with airway remodeling, inflammation and FEV1 decline in asthma patients and assess whether ICS 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/VC were tested. FEV1 and VC data were collected in 281 asthmatics with 30-year follow-up (population 2). Linear Mixed Effect Models assessed associations of SNPs with FEV1 decline. Seven of the 17 SNPs were associated with airway remodeling, 3 with CD8+T-cell numbers, 2 with eosinophil counts and 7 with FEV1 decline. All associations occurred only in patients using ICS. In general, alleles associated with less remodeling correlated with less FEV1 decline and higher FEV1/VC. Decreased epithelial E-cadherin expression was associated with 5 SNPs in no 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 remodeling and lung function in asthma. These effects are modified by the use of inhaled corticosteroids.


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CRRD Object Information
CRRD ID: 5132878
Created: 2011-06-03
Species: All species
Last Modified: 2011-06-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.