CFTR gene mutations and asthma in the Norwegian Environment and Childhood Asthma study

• Published in: Respiratory medicine 2006-12, Vol.100 (12), p.2121-2128
• Main Authors: Munthe-Kaas, Monica Cheng, Lødrup Carlsen, Karin C., Carlsen, Kai-Håkon, Skinningsrud, Beate, Håland, Geir, Devulapalli, Chandra Sekhar, Pettersen, Morten, Eiklid, Kristin
• Format: Article
• Language: English
• Subjects: Asthma; Asthma - epidemiology; Asthma - genetics; Asthma - physiopathology; Biological and medical sciences; Breath Tests; Bronchial Hyperreactivity - physiopathology; Bronchial hyperresponsiveness; CFTR; Child; Chronic obstructive pulmonary disease, asthma; Cystic fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Errors of metabolism; Female; Forced Expiratory Volume; Genes; Genetic analysis; Haplotypes - genetics; Heterozygote; Humans; Lung - physiopathology; Lung function; Male; Medical sciences; Metabolic diseases; Metabolic disorders; Miscellaneous hereditary metabolic disorders; Mutation; Mutation - genetics; Nitric Oxide - analysis; Norway - epidemiology; Pneumology; Polymorphism, Genetic - genetics; Prospective Studies
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2006.03.026

Several candidate genes have been implicated in the etiology of asthma, including the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Mutations in the CFTR gene result in derangements of mucociliary clearance. Homozygotes for CFTR mutations develop cystic fibrosis (CF), a disorder characterized mainly by lung and pancreas disease. To investigate whether there was an increased frequency of CFTR mutations in asthma patients. Seven hundred and three subjects aged 10–11 years from the environment and childhood asthma (ECA) study were included in the present study. Possible associations between asthma, reduced lung function, bronchial hyperresponsiveness (BHR), and increased or decreased nitrogen oxide (NO) levels (based on structural parental interview, spirometry, PD 20 methacholine challenge test and exhaled NO measurements), and the five most common CFTR mutations in Norway (ΔF508, R117H, R117C, 4005+2T→C, 394delTT), the modulating polymorphisms IVS8(TG) m T n and the IVS8-5T were investigated. No association were found between asthma, reduced lung function, BHR or exhaled NO levels and CF heterozygosity. However, the IVS8(TG) 11T 7 haplotype was associated with normal lung function. Our results do not support the hypothesis that CFTR mutations or polymorphisms play a role in the pathogenesis of asthma in children. However, the distribution of Tn(TG)m haplotypes differed between individuals with reduced lung function and individuals with normal lung function.