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Respir Res. 2008 May 28;9:46. doi: 10.1186/1465-9921-9-46.

Could a defective epithelial sodium channel lead to bronchiectasis.

Author information

  • 1Service d'Explorations Fonctionnelles, AP-HP, Hôpital Cochin, Paris, France. ifajac@cochin.univ-paris5.fr

Abstract

BACKGROUND:

Bronchiectasis is defined as a permanent dilation of the airways arising from chronic bronchial inflammation/infection. In 50% of cases, no etiology can be identified. Recently, the role of the epithelial sodium channel ENaC has been pointed out in the pathophysiology of cystic fibrosis, a disease due to mutations in the CFTR gene and causing bronchiectasis in the airways. Moreover, it was found that transgenic mice overexpressing ENaCbeta present cystic fibrosis-like lung disease symptoms. Our aim was to evaluate if a defective ENaC protein could be involved in the development of bronchiectasis.

METHODS:

We extensively analysed ENaCbeta and gamma genes in 55 patients with idiopathic bronchiectasis and without two mutations in the coding regions of CFTR. Thirty-eight patients presented functional abnormalities suggesting impaired sodium transport (abnormal sweat chloride concentration or nasal potential difference measurement), and 17 had no such evidence.

RESULTS:

Sequencing of the exons and flanking introns of the ENaCbeta and gamma gene identified five different amino-acid changes (p.Ser82Cys, p.Pro369Thr, p.Asn288Ser in ENaCbeta ; and p.Gly183Ser, p.Glu197Lys in ENaCgamma) in heterozygous state in 8 patients. The p.Ser82Cys amino-acid change was found in 3 unrelated patients who were also heterozygous for a CFTR mutation or variant (1 p.F508del, 1 IVS8-5T, and 1 IVS8-5T:1716G>A (p.E528E)). The other mutations were found in patients without CFTR mutation, the p.Glu197Lys mutation in 2 patients and the other variants in single patients. Among the 8 patients bearing an ENaC mutation, 5 had functional abnormalities suggesting impaired sodium transport.

CONCLUSION:

Our results suggest that several variants in ENaCbeta and gamma genes might be deleterious for ENaC function and lead to bronchiectasis, especially in patients who are trans-heterozygotes for ENaCbeta/CFTR mutations or variants.

PMID:
18507830
[PubMed - indexed for MEDLINE]
PMCID:
PMC2435537
Free PMC Article
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