Nitric oxide synthase 1 as a potential modifier gene of decline in lung function in patients with cystic fibrosis

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 rol...

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Bibliographic Details
Published in:Thorax Vol. 59; no. 2; pp. 156 - 158
Main Authors: Texereau, J, Marullo, S, Hubert, D, Coste, J, Dusser, D J, Dall’Ava-Santucci, J, Dinh-Xuan, A T
Format: Journal Article
Language:English
Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.02.2004
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Subjects:
Adult
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Biological and medical sciences
Body mass index
Cardiology. Vascular system
Cystic Fibrosis
Cystic Fibrosis - enzymology
Cystic Fibrosis - genetics
Cystic Fibrosis - physiopathology
Dinucleotide Repeats - genetics
Female
Forced Expiratory Volume - genetics
Gastroenterology. Liver. Pancreas. Abdomen
Genes
genetics
Genotype & phenotype
Humans
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Lung diseases
lung function
Male
Medical sciences
Mutation
Nitric oxide
Nitric Oxide - analysis
Nitric Oxide Synthase - genetics
nitric oxide synthase 1 (NOS1) gene
Nitric Oxide Synthase Type I
Other diseases. Semiology
Pneumology
polymorphism
Polymorphism, Genetic - genetics
Human
Respiratory disease
Enzyme
Metabolic diseases
Cystic fibrosis
Potential
Nitric-oxide synthase
Genetic disease
Lung function
Gene
Digestive diseases
Anesthesia
Oxidoreductases
Circulatory system
Cardiology
Pancreatic disease
ISSN:0040-6376, 1468-3296
Online Access:Get full text
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Summary: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.
Bibliography:PMID:14760158
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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
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ISSN:0040-6376
1468-3296
DOI:10.1136/thorax.2003.006718