title: Chloride transport in nasal ciliated cells of cystic fibrosis heterozygotes.
abstract: Studying subjects heterozygous for mutations of the cystic fibrosis (CF) gene may help clarify the impact on disease onset of CF transmembrane conductance regulator protein (CFTR-)-dependent chloride secretion. CFTR-mediated chloride transport was evaluated in 52 heterozygous subjects, 32 healthy control subjects, and 77 patients with CF with class I or II mutations. We measured the change in nasal potential difference in response to chloride-free isoproterenol solution for each subject and used a video-imaging fluorescent dye assay to assess the percentage of nasal ciliated cells with cAMP-dependent anion conductance. Our findings did not confirm the standard assumption that heterozygosity implies 50% of normal CFTR function. Half the heterozygous subjects had CFTR-mediated chloride transport levels below 50% of the normal range, and one-third had levels similar to those of the patients with CF. This reduced CFTR function was not associated with an elevated prevalence of CF-like symptoms in heterozygous subjects but was highly related to respiratory status in the patients with CF. These data suggest that CFTR-dependent chloride conductance does not directly modulate disease severity but may be part of a more global defect in patients with CF involving other CFTR functions or currently unknown modulatory factors.
authors.affiliation: Centre de Ressources et de Compétences en Mucoviscidose, Laboratoire d'Explorations Fonctionnelles Rénales, Service de Biochimie A, Service d'ORL, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sermet-Gaudelus
authors.forename: Michèle
authors.initials: M
authors.lastname: Déchaux
authors.forename: Benoît
authors.initials: B
authors.lastname: Vallée
authors.forename: Anne
authors.initials: A
authors.lastname: Fajac
authors.forename: Emanuelle
authors.initials: E
authors.lastname: Girodon
authors.forename: Thao
authors.initials: T
authors.lastname: Nguyen-Khoa
authors.forename: Rémi
authors.initials: R
authors.lastname: Marianovski
authors.forename: Ilse
authors.initials: I
authors.lastname: Hurbain
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Bresson
authors.forename: Gérard
authors.initials: G
authors.lastname: Lenoir
authors.forename: Aleksander
authors.initials: A
authors.lastname: Edelman
mesh_terms: D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008564:Membrane Potentials; D009154:Mutation; D009297:Nasal Mucosa / Q000378:metabolism*
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator