Is the hemochromatosis gene a modifier locus for cystic fibrosis?
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.
Rohlfs
E M
EM
Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill 27599, USA.
Shaheen
N J
NJ
Silverman
L M
LM
D000328:Adult; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics*; D006801:Humans; D007415:Intestinal Obstruction / Q000209:etiology* / Q000235:genetics; D008297:Male; D008470:Meconium; D017384:Sequence Deletion
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator