title: Hemochromatosis gene mutations and iron metabolism in celiac disease.
abstract: OBJECTIVE
  Iron deficiency anemia is a common manifestation of celiac disease, which may be due to genetic and environmental factors. HFE mutations, frequent in Caucasian populations, can cause increased intestinal iron absorption and thus could protect against the development of iron deficiency. The aim of this study was to evaluate the prevalence of HFE mutations and their effect on iron metabolism in Italian celiac patients at diagnosis and after a gluten-free diet.
  
  
  METHODS
  C282Y and H63D mutations were assessed by polymerase chain reaction (PCR) and restriction enzyme digestion in 203 patients with celiac disease and in 206 controls. HLA alleles were determined by sequence-specific primers and PCR. Duodenal histology was graded using Marsh's classification, and iron parameters measured by standard techniques.
  
  
  RESULTS
  The frequency of the C282Y mutation was similar in celiac patients and controls (0.034 vs. 0.031); comparable frequencies were detected also for the H63D allele (0.170 vs. 0.136 in celiac patients and controls, respectively). Neither of the two HFE mutations affected iron indices in celiac patients at diagnosis, whereas a significant inverse correlation was detected between hemoglobin or ferritin and severity of histological damage (Marsh 3C or 3B vs. 3A, p<0.05 for both parameters). After a gluten-free diet, a slight increase in hemoglobin levels was observed in C282Y carriers as compared to controls, but only in female patients (p=0.044).
  
  
  CONCLUSIONS
  In Italian patients with untreated celiac disease, HFE mutations do not constitute a protective factor against the development of iron deficiency, which seems to be mainly determined by the severity of the intestinal lesions.
authors.affiliation: Department of Experimental and Environmental Medicine and Medical Biotechnology, University of Milano Bicocca, via Cadore 48, 20052, Monza, Milan, Italy. donatella.barisani@unimib.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Barisani
authors.forename: Stefano
authors.initials: S
authors.lastname: Ceroni
authors.forename: Silvia
authors.initials: S
authors.lastname: Del Bianco
authors.forename: Raffaella
authors.initials: R
authors.lastname: Meneveri
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bardella
mesh_terms: D000328:Adult; D000483:Alleles; D002446:Celiac Disease / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D005983:Glutens; D006680:HLA Antigens / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D006454:Hemoglobins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D006454:Hemoglobins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005983:Glutens; D005293:Ferritins; D007501:Iron