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

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 Preliminary unpublished data and anecdotal information from CF families suggested that, remarkably, the ΔF508 allele might protect heterozygotes against bronchial asthma prompted us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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References

  1. 1

    Tizzano, E.F. & Buchwald, M. Cystic fibrosis: Beyond the gene to therapy. J. Pediat. 120, 337–349 (1992).

    CAS  Article  Google Scholar 

  2. 2

    Lemna, W.K. et al. Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis. New Engl. J. Med. 322, 291–296 (1990).

    CAS  Article  Google Scholar 

  3. 3

    Morral, N. et al. The origin of the major cystic fibrosis mutation (ΔF508) in European populations. Nature Genet. 7, 169–175 (1994).

    CAS  Article  Google Scholar 

  4. 4

    Davis, P.B. & Vargo, K. Pulmonary abnormalities in obligate heterozygotes for cystic fibrosis. Thorax 42, 120–125 (1987).

    CAS  Article  Google Scholar 

  5. 5

    Davis, P.B. & Byard, P.J. Heterozygotes for cystic fibrosis: Models for study of airway and autonomic reactivity. J. appl. Physiol. 66, 2124–2128 (1989).

    CAS  Article  Google Scholar 

  6. 6

    Gyurkovitz, K., Markus, V. & Bittera, I. Cystic fibrosis heterozygosity in childhood bronchial asthma. Lancet 1, 203 (1977).

    Article  Google Scholar 

  7. 7

    American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am. Rev. resp. Dis. 136, 225–244 (1977).

  8. 8

    National Asthma Education Program. Guidelines for the diagnosis and management of asthma. (National Institutes of Health, Bethesda, MD, 1991. DHMS publication no. NIH 91-3042).

  9. 9

    Swift, M., Kupper, L.L. & Chase, C.L. Effective testing of gene-disease associations. Am. J. hum. Genet. 47, 266–274 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Pignatti, P.F., Bombieri, C., Marigo, C., Benetazzo, M. & Luisetti, M. Increased incidence of cystic fibrosis gene mutations in adults with disseminated bronchiectasis. Hum. molec. Genet. 4, 635–639 (1995).

    CAS  Article  Google Scholar 

  11. 11

    Counahan, R. & Mearns, M.B. Prevalence of atopy and exercise-induced bronchial lability in relatives of patients with cystic fibrosis. Archs Dis. Childh. 50, 477–481 (1975).

    CAS  Article  Google Scholar 

  12. 12

    Bonforte, R.J. Pneumonia of infancy, in Pediatric Respiratory Disease (ed. Hilman, B.) Ch. 30, p. 263 (Saunders, Philadelphia, 1993).

    Google Scholar 

  13. 13

    Baxter, P.S., Goldhill, J., Hardcastle, J., Hardcastle, P.T. & Taylor, C.J. Accounting for cystic fibrosis. Nature 335, 211 (1988).

    CAS  Article  Google Scholar 

  14. 14

    Quinton, P.M. Cystic fibrosis: A disease in electrocyte transport. FASEB J. 4, 2709–2717 (1990).

    CAS  Article  Google Scholar 

  15. 15

    Friedman, K.J., Highsmith, W.E. & Silverman, L.M. Detecting multiple cystic fibrosis mutations by polymerase chain reaction-mediated site-directed mutagenesis. Clin. Chem. 37, 753–755 (1991).

    CAS  PubMed  Google Scholar 

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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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