The pathogenic consequences of a single mutated CFTR gene.

Background. Cystic fibrosis is a recessive disorder mainly characterized by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis DF508 mutation are at risk of obstructive pulmonary disease. Methods. We studied a cross-sectional sample from the general population of Copenhagen, Denmark, aged 20 years and older. We did spirometry to measure forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC), and did genotyping on blood samples of 9141 individuals. We asked for information on smoking and other factors that could have contributed to obstructive pulmonary disease. Findings. We identified 250 carriers of the DF508 mutation (2.7% [95% CI 2.5 to 3.1]). 9% of carriers reported having asthma compared with 6% of non-carriers (p= 0.04). The odds ratio for asthma in participants heterozygous for DF508 mutations was 2.0 (1.2 to 3.5, p=0.02). Furthermore, among individuals with airway obstruction, the percentage predicted FEV1 and FVC were significantly lower in participants heterozygous for DF508 than in non-carriers (49 vs 58%, p=0.004; and 70 vs 82%, p<0.001, respectively), mainly due to an effect in those with self-reported asthma. Interpretation. Cystic fibrosis DF508 heterozygosity may be over-represented among people with asthma and seems to be associated with decreased pulmonary function in people with airway obstruction who also have asthma. (Lancet 1998;351:1911–3)