Cystic
fibrosis
Thorax 2004;59:156-158 © 2004 BMJ Publishing
Group Ltd & British Thoracic Society
CYSTIC FIBROSIS
Nitric oxide synthase 1 as a potential modifier gene of decline in lung
function in patients with cystic fibrosis
J Texereau1, S Marullo2, D Hubert3, J Coste4, D J Dusser3, J Dall’Ava-Santucci1
and A T Dinh-Xuan1
1 Service de Physiologie-Explorations Fonctionnelles, Hôpital Cochin,
AP-HP, Université Paris 5, Paris, France
2 Department of Cell Biology, Institut Cochin, INSERM, CNRS, Paris, France
3 Service de Pneumologie, Hôpital Cochin, AP-HP, Université Paris 5, Paris,
France
4 Service d’Informatique Médicale et de Biostatistiques, Hôpital Cochin,
AP-HP, Université Paris 5, Paris, France
Correspondence to: Professor A T Dinh-Xuan
Service de Physiologie-Explorations Fonctionnelles, Hôpital Cochin, 27
rue du faubourg Saint-Jacques, 75014 Paris, France; anh-tuan.dinh-xuan@cch.ap-hop-paris.fr
ABSTRACT
Background: The severity of lung disease varies widely
in patients with cystic fibrosis (CF) who have the same type of mutations
of the cystic fibrosis transmembrane regulator (CFTR) gene, suggesting
involvement of "modifier" genes. The nitric oxide synthase 1
(NOS1) gene is a candidate for this role because exhaled nitric oxide
(NO) is reduced in patients with CF and NOS1 activity contributes to transepithelial
ionic transport, immune defence, and non-specific inflammation of the
airways.
Methods: Dinucleotide GT repeat polymorphism was studied
in the 5' untranslated region of the NOS1 gene, immediately upstream from
the transcription initiation site, in 59 patients with CF and 59 healthy
controls.
Results: Nineteen alleles of the NOS1 gene were identified
according to the number of GT repeats (from 18 to 36) in the 5 untranslated
region. Exhaled NO levels were significantly correlated with the number
of GT repeats. Patients with CF who had the NOS1 genotype associated with
high NO production had a slower decline in lung function during the 5
year follow up period. There was no confounding effect of age, chronic
bacterial colonisation of the airway, or CFTR genotype.
Conclusions: These data suggest a possible link between
the NOS1 gene locus and the rate of decline in lung function in patients
with CF.
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