Protection against bronchial asthma by CFTR ΔF508 mutation: A heterozygote advantage in cystic fibro

Abstract

Cystic fibrosis (CF) is a multisystem autosomal recessive disorder caused by mutations of the cystic fibrosis transmembrane regulator (CFTR), a protein that regulates cyclic-AMP-media ted chloride conductance at the apical membrane of secretory epithelia1. Mutations in the CFTR gene are common in many populations. In North America, 4–5% of the general population are heterozygous for a CFTR mutation2. Although there are over 400 known CFTR mutations, a single mutation, a deletion of the phenylalanine at position 508 (ΔF508) in exon 10, accounts for about 70% of all CF chromosomes worldwide3. The reasons for the high frequency of the ΔF508 CFTR allele — the selective advantage associated with CF heterozygosity — are unknown1. Many physiological abnormalities have been observed in CF heterozygotes4–6, although the clinical significance of these observations is unknown. Preliminary unpublished data and anecdotal information from CF families suggested that, remarkably, the ΔF508 allele might protect heterozygotes against bronchial asthma prompted us to further investigate this possibility. Here we present evidence that the ΔF508 CF allele protects against asthma in childhood and early adult life.

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Schroeder, S., Gaughan, D. & Swift, M. Protection against bronchial asthma by CFTR ΔF508 mutation: A heterozygote advantage in cystic fibrosis. Nat Med 1, 703–705 (1995). https://doi.org/10.1038/nm0795-703

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