CFTR gene mutations - including three novel nucleotide substitutions - andhaplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease

In order to investigate the incidence of cystic fibrosis transmembrane cond uctance regulator (CFTR) gene mutations and unclassified variants in chroni c pulmonary disease in children and adults, we studied 20 patients with ast hma, 19 with disseminated bronchiectasis (DB I of unknown aetiology, and 12 , patients with chronic obstructive pulmonary disease (COPD), and compared the results to 52 subjects from the general Greek population. Analysis of t he whole coding region of the CFTR gene and its flanking intronic regions r evealed that the proportion of CFTR mutations was 45% in asthma (P<0.05), 2 6.3% in DB (P>0.05), 16.7% in COPD (P>0.05), compared to 15.4% in the gener al population. Seventeen different molecular defects involved in disease pr edisposition were identified in 16 patients. Three potentially disease-caus ing mutations, T388 M, M1R and V111, are novel, found so far only in three asthma patients. The hyperactive M470 allele was found more frequently in C OPD patients (frequency 70.8%, P<0.01) than in the controls. The study of t he TGmTnM470 V polyvariant CFTR allele revealed the presence of CFTR functi on-modulating haplotypes TG13/T5/M470. TG11/T5/M470, TG12/T5/V470 and TG12/ T7, combined with M470 or V470, in six asthma patients, four DB patients (P <0.01), and two COPD patients (P<0.05). These results confirm the involveme nt of the CFTR gene in asthma, DB and possibly in COPD.