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 entireCF population); 19 (23.2%)wereH63D 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.
History
Publication title
Respirology
Volume
15
Pagination
141-149
ISSN
1323-7799
Department/School
Menzies Institute for Medical Research
Publisher
Blackwell Publishing Asia
Place of publication
54 University St, P O Box 378, Carlton, Australia, Victoria, 3053
Rights statement
The definitive published version is available online at: http://onlinelibrary.wiley.com/