title: HFE gene mutation and oxidative damage biomarkers in patients with myelodysplastic syndromes and its relation to transfusional iron overload: an observational cross-sectional study.
abstract: OBJECTIVE
  A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated.
  
  
  METHODS
  An observational cross-sectional study involving 87 healthy individuals and 78 patients with myelodysplastic syndromes (MDS) with and without IOL, seen at University Hospital of the Federal University of Ceará, Brazil, between May 2010 and September 2011.
  
  
  METHODS
  IOL was defined using repeated measures of serum ferritin ≥1000 ng/mL. Variations in the HFE gene were investigated using PCR/restriction fragment length polymorphism (RFLP). The biomarkers of oxidative stress (plasmatic malonaldehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were determined by spectrophotometry.
  
  
  RESULTS
  The HFE gene variations were identified in 24 patients (30.77%) and 5 volunteers (5.74%). The H63D variant was observed in 35% and the C282Y variant as heterozygous in 5% of patients with MDS with IOL. One patient showed double heterozygous variant (C282Y/H63D) and serum ferritin of 11,649 ng/mL. In patients without IOL, the H63D variant was detected in 29.34%. Serum MDA levels were highest in patients with MDS with IOL, with a significant difference when compared with patients without IOL and healthy volunteers, pointing to the relationship between IOL and oxidative stress. The GPx and SOD were also significantly higher in these patients, indicating that lipid peroxidation increase was followed by an increase in antioxidant capacity. Higher ferritin levels were observed in patients with HFE gene variation. 95.7% of patients with MDS with the presence of HFE gene variations had received more of 20 transfusions.
  
  
  CONCLUSIONS
  We observed a significant increase in MDA levels in patients with MDS and IOL, suggesting an increased lipid peroxidation in these patients. The accumulation of MDA alters the organisation of membrane phospholipids, contributing to the process of cellular degeneration. Results show that excess iron intensifies the process of cell damage through oxidative stress.
  
  
  BACKGROUND
  Local Ethics Committee (licence 150/2009).
authors.affiliation: Post-Graduate Program in Medical Science, Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil Cancer Cytogenomic Laboratory, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Geane Felix
authors.initials: GF
authors.lastname: De Souza
authors.affiliation: Post-Graduate Program in Medical Science, Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil Cancer Cytogenomic Laboratory, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Howard Lopes
authors.initials: HL
authors.lastname: Ribeiro
authors.affiliation: Post-Graduate Program in Medical Science, Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil Cancer Cytogenomic Laboratory, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Juliana Cordeiro
authors.initials: JC
authors.lastname: De Sousa
authors.affiliation: Cancer Cytogenomic Laboratory, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Fabíola Fernandes
authors.initials: FF
authors.lastname: Heredia
authors.affiliation: Department of Pharmacia, Federal University of Piauí, Teresina, Piauí, Brazil.
authors.forename: Rivelilson Mendes
authors.initials: RM
authors.lastname: De Freitas
authors.affiliation: Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Manoel Ricardo Alves
authors.initials: MR
authors.lastname: Martins
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Romélia Pinheiro
authors.initials: RP
authors.lastname: Gonçalves
authors.affiliation: Cancer Cytogenomic Laboratory, Federal University of Ceara, Fortaleza, Ceara, Brazil Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Ronald Feitosa
authors.initials: RF
authors.lastname: Pinheiro
authors.affiliation: Cancer Cytogenomic Laboratory, Federal University of Ceara, Fortaleza, Ceara, Brazil Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Silvia Maria Meira
authors.initials: SM
authors.lastname: Magalhães
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000150:complications / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D015415:Biomarkers; D015395:Histocompatibility Antigens Class I
keywords: Hemochromatosis; Iron overload; Myelodysplastic syndromes; Oxidative stress
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