title: H63D mutation in the HFE gene increases iron overload in beta-thalassemia carriers.
abstract: OBJECTIVE
  Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism. The HFE gene implicated in this disorder has been identified on chromosome 6 (6p21.3). The most prevalent mutation in HH patients changes the 282 cysteine residue to tyrosine (C282Y). The role of a second mutation which changes the 63 histidine to aspartic acid (H63D) in iron overload has been controversial. The aim of this study was to evaluate the effect of the H63D mutation on the ferritin levels of beta-thalassemia carriers.
  
  
  METHODS
  beta-thalassemia carriers have a tendency to increase iron absorption because of mild anemia and slightly increased erythropoiesis. Differences in ferritin levels between homozygotes for H63D and wild type may indicate a modulator effect of the HFE mutation on iron absorption. We studied 152 healthy males, heterozygous for beta-thalassemia. Serum ferritin was measured by chemiluminescence. H63D genotypes were determined by digestion of polymerase chain reaction (PCR) products with MboI restriction enzyme.
  
  
  RESULTS
  Forty-five subjects were H63D heterozygotes and four subjects were H63D homozygotes. Ferritin levels were (mean +/- SD): 250 +/- 138 microg/L in homozygotes for the wild type H/H; 295 +/- 186 microg/L in H/D heterozygotes; and 389 +/- 75 microg/L in homozygotes for the mutation D/D. The difference in ferritin values between H/H and D/D is statistically significant (p=0.022).
  
  
  CONCLUSIONS
  beta-thalassemia carriers who are homozygotes for the H63D mutation have higher ferritin levels than beta-thalassemia carriers with the H/H genotype, suggesting that the H63D mutation may have a modulating effect on iron absorption.
authors.affiliation: Dipartimento Scienze Biomediche e Biotecnologie, Sezione Clinica e Biología dell'Età Evolutiva, Università degli Studi di Cagliari, Italy. amelis@mcweb.unica.it
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Melis
authors.forename: Milena
authors.initials: M
authors.lastname: Cau
authors.forename: Federica
authors.initials: F
authors.lastname: Deidda
authors.forename: Susanna
authors.initials: S
authors.lastname: Barella
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
mesh_terms: D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000150:complications* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D019190:Iron Overload / Q000209:etiology / Q000235:genetics*; D008297:Male; D008664:Metal Metabolism, Inborn Errors / Q000235:genetics; D017354:Point Mutation; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics / Q000378:metabolism*
chemical_list: D005293:Ferritins