Population-based study of cystic fibrosis disease severity and haemochromatosis gene mutations

  1. Upasna PRATAP,
  2. Stephen QUINN,
  3. Leigh B. BLIZZARD,
  4. David W. REID

Article first published online: 27 DEC 2009

DOI: 10.1111/j.1440-1843.2009.01649.x

Issue

Respirology

Respirology

Volume 15, Issue 1, pages 141–149, January 2010

Additional Information

How to Cite

PRATAP, U., QUINN, S., BLIZZARD, L. B. and REID, D. W. (2010), Population-based study of cystic fibrosis disease severity and haemochromatosis gene mutations. Respirology, 15: 141–149. doi: 10.1111/j.1440-1843.2009.01649.x

Author Information

  1. Respiratory Research Group, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia

*David Reid, University of Tasmania Medical School, Collins Street, Hobart, Tas. 7001, Australia. Email: d.e.c.reid@utas.edu.au

Publication History

  1. Issue published online: 27 DEC 2009
  2. Article first published online: 27 DEC 2009
  3. Received 23 March 2009; invited to revise 11 June 2009; revised 27 July 2009; accepted 12 August 2009 (Associate Editor: Yuben Moodley).

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Keywords:

  • cystic fibrosis;
  • haemochromatosis;
  • iron;
  • Pseudomonas aeruginosa

Disease outcomes in CF may be very variable despite identical genotypes, environments and infecting organisms. This study provides evidence to support a disease-modifying role for haemochromatosis gene mutations. These effects are most likely mediated through alterations in systemic iron homeostasis.

ABSTRACT

Background and objective:  Haemochromatosis (HFE) mutations increase the risk of bowel obstruction in cystic fibrosis (CF), but the impact on other disease manifestations is unknown.

Methods:  We determined the prevalence of HFE mutations (C282Y and H63D) in the Tasmanian CF population and assessed the relationship to systemic iron stores, Pseudomonas aeruginosa infection, lung disease severity and prevalence of diabetes.

Results:  DNA was obtained from 82 individuals (96% of the entire CF population); 19 (23.2%) were H63D heterozygotes, three (3.7%) were H63D homozygotes and two patients were compound C282Y/H63D (2.4%). Seven (8.5%) patients were heterozygous for the C282Y mutation. Overall, 31 (37.8%) patients carried a HFE mutation. CF patients possessing HFE mutations had significantly better iron stores than non-carriers (P < 0.05). The mean slopes of annual decline in FEV1 and FVC % predicted were significantly steeper in HFE carriers compared with non-carriers (P < 0.01). Patients with HFE mutations were more likely to have had childhood bowel obstruction (RR 2.44, 95% CI: 1.04–5.74, P < 0.05). Diabetes was more common in HFE carriers (RR 2.96, 95% CI: 0.99–8.8, P = 0.05), but this effect attenuated when corrected for age (RR 2.89, 95% CI: 0.91–9.21, P = 0.07).

Conclusions: HFE gene mutations modify disease severity in CF, through probable effects on iron homeostasis.

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