Cystic Fibrosis: Modifier Genes


Cystic fibrosis (CF) is a rare autosomal recessive disease that causes early death through respiratory failure. Although it is known that CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) it has been found that other genetic factors make a large contribution to the severity of lung disease as well as several other CF traits. Several large‐scale genomewide association studies have been performed for CF lung disease severity, body mass index/nutritional status, CF‐related diabetes, meconium ileus and age of onset of chronic Pseudomonas aeruginosa infection. Several genes have been identified that modulate CF disease severity. In particular, apical membrane constituents have been associated with several phenotypes including lung function, meconium ileus and age of onset of P. aeruginosa infection. The results of these studies have provided insight into the pathophysiology of CF and have identified novel therapeutic targets.

Key Concepts

  • Lung disease severity in CF, along with several other CF traits, is influenced by non‐CFTR genetic factors.
  • Genomewide association studies and linkage analysis have identified several genes associated with CF severity.
  • Meta‐analysis of several patient cohorts is required to identify reproducible findings.
  • Apical membrane constituents, in particular SLC6A14, SLC26A9 and SLC9A3, are a class of molecules associated with several CF phenotypes.
  • Exome‐wide sequencing can be used as an alternative approach to discover novel modifier genes.

Keywords: cystic fibrosis; modifier genes; genomewide association study; lung disease severity; meconium ileus

Figure 1. Apical membrane constituents that are associated with CF related traits.


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Further Reading

Brennan ML and Schrijver I (2016) Cystic fibrosis: a review of associated phenotypes, use of molecular diagnostic approaches, genetic characteristics, progress, and dilemmas. Journal of Molecular Diagnostics 18 (1): 3–14.

Chang EH and Zabner J (2015) Precision genomic medicine in cystic fibrosis. Clinical and Translational Science 8 (5): 606–610.

Corvol H, Thompson KE, Tabary O, le Rouzic P and Guillot L (2016) Translating the genetics of cystic fibrosis to personalized medicine. Translational Research 168: 40–49.

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Saferali, Aabida, Turvey, Stuart E, and Sandford, Andrew J(Sep 2016) Cystic Fibrosis: Modifier Genes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020233]