title: The influence of hemochromatosis mutations on iron overload of thalassemia major.
abstract: OBJECTIVE
  Hemochromatosis is a genetic form of iron overload due to a defective HFE gene. Secondary iron overload is the main complication in transfusion-dependent thalassemia patients. In this work we have examined the prevalence of HFE mutations in thalassemia major and evaluated the degree of iron overload of patients with and without HFE mutations.
  
  
  METHODS
  HFE mutations were studied in 71 Italian thalassemic patients and in 189 normal controls, using PCR and restriction enzyme analysis. The degree of iron overload, assessed by serum ferritin and liver iron concentration (LIC), was compared in 17 patients with mutations in the HFE gene, and in 17 subjects with wild type HFE genotype. The two groups of patients had comparable globin gene mutations, were matched for age and were homogeneous for transfusion and chelation history. In all cases the iron balance calculated on the basis of transfusion regimen and iron excreted by chelation was available.
  
  
  RESULTS
  The allele frequencies of C282Y and H63D were respectively 1.4% and 12.7% in patients and 1.1% and 11.4% in controls. No case of C282Y homozygosity was recorded among patients. No significant difference was found in terms of serum ferritin, LIC, or the age at chelation start between patients with and without HFE mutations. The single patient with H63D homozygosity was severely iron-loaded.
  
  
  CONCLUSIONS
  Our data suggest that the presence of a single mutation in the HFE gene does not influence the severity of iron loading in thalassemia patients following a regular transfusion and chelation program.
authors.affiliation: Dipartimento di Scienze Pediatriche, Università di Torino, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Longo
authors.forename: G
authors.initials: G
authors.lastname: Zecchina
authors.forename: L
authors.initials: L
authors.lastname: Sbaiz
authors.forename: R
authors.initials: R
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Piga
authors.forename: C
authors.initials: C
authors.lastname: Camaschella
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001803:Blood Transfusion; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007223:Infant; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D017354:Point Mutation; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications* / Q000628:therapy
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins