Population-based study of cystic fibrosis disease severity and haemochromatosis gene mutations.
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.
Pratap
Upasna
U
Respiratory Research Group, Menzies Research Institute, University of Tasmania, Hobart, Tasmania 7001, Australia.
Quinn
Stephen
S
Blizzard
Leigh B
LB
Reid
David W
DW
D000293:Adolescent; D000328:Adult; D003550:Cystic Fibrosis / Q000453:epidemiology* / Q000235:genetics*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D015995:Prevalence; D011552:Pseudomonas Infections / Q000453:epidemiology / Q000235:genetics; D011550:Pseudomonas aeruginosa; D012720:Severity of Illness Index; D013648:Tasmania / Q000453:epidemiology; D055815:Young Adult
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron