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Is the hemochromatosis gene a modifier locus for cystic fibrosis?
E M Rohlfs1, N J Shaheen, L M Silverman
1Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill 27599, USA.
Insights
The HFE gene may influence meconium ileus in cystic fibrosis (CF) patients. Carrier frequency of the C282Y mutation differed between CF patients with meconium ileus and controls, suggesting a potential link.
Area of Science:
- Genetics
- Medical Genetics
- Molecular Biology
Background:
- Cystic Fibrosis (CF) presents with variable clinical manifestations, indicating the role of modifier genes.
- Meconium ileus, a common CF complication in neonates, lacks determined genetic or environmental causative factors.
- The HFE gene is proposed as a candidate modifier locus for CF due to its proximity to HLA loci and similarities in gastrointestinal manifestations with hereditary hemochromatosis.
Purpose of the Study:
- To investigate the HFE gene as a potential modifier locus influencing meconium ileus in cystic fibrosis patients.
- To determine the frequency of C282Y and H63D mutations in CF patients homozygous for delta F508 with known meconium ileus status.
Main Methods:
- Genotyping for C282Y and H63D mutations in the HFE gene.
- Analysis of mutation frequencies in 89 cystic fibrosis patients (homozygous for delta F508) stratified by meconium ileus status.
- Comparison of mutation frequencies between CF patient groups and an unaffected control group.
Main Results:
- A significant difference in C282Y carrier frequency was observed between CF patients with meconium ileus (19.4%) and the unaffected control group (7.7%).
- The difference in C282Y carrier frequency between meconium ileus and non-meconium ileus CF patient groups was not statistically significant (19.4% vs. 10.3%).
- No significant difference in H63D mutation frequency was found among the studied groups.
Conclusions:
- The study suggests a potential relationship between the HFE gene and the development of meconium ileus or other gastrointestinal complications in cystic fibrosis.
- Further investigation with larger patient cohorts is warranted to confirm the role of the HFE gene in CF pathogenesis.
- The HFE gene warrants further study as a potential genetic modifier in cystic fibrosis.
Abstract:
The variable clinical manifestations of cystic fibrosis (CF) suggest the influence of modifier genes. For example, meconium ileus is present in approximately 10-15% of neonates with cystic fibrosis; however, the genetic and, or environmental factors that determine whether an individual will develop this complication have not been determined. We propose the HFE gene as a candidate modifier locus for CF based on (1) the suggestion of an association between the HLA loci and CF phenotypes; (2) the location of the HFE gene near the HLA loci and; (3) the similarity between the gastrointestinal manifestations of hereditary hemochromatosis and CF. We have determined the frequency of the C282Y and H63D mutations in a group of 89 CF patients who were homozygous for delta F508 and for whom meconium ileus status was known. The carrier frequency of C282Y among the CF patients with meconium ileus was significantly different from that of our unaffected control group (19.4% versus 7.7%). However, the difference between the meconium ileus and the nonmeconium ileus groups was not significant (19.4% versus 10.3%). There was no difference in the frequency of the H63D among the three groups that were studied. These data are suggestive of a relationship between the development of meconium ileus or other gastrointestinal diseases in CF and the HFE gene. Further study of a larger group of patients is warranted.