RT Journal Article
SR Electronic
T1 HFE gene mutation and oxidative damage biomarkers in patients with myelodysplastic syndromes and its relation to transfusional iron overload: an observational cross-sectional study
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e006048
DO 10.1136/bmjopen-2014-006048
VO 5
IS 4
A1 Geane Felix De Souza
A1 Howard Lopes Ribeiro, Jr
A1 Juliana Cordeiro De Sousa
A1 Fabíola Fernandes Heredia
A1 Rivelilson Mendes De Freitas
A1 Manoel Ricardo Alves Martins
A1 Romélia Pinheiro Gonçalves
A1 Ronald Feitosa Pinheiro
A1 Silvia Maria Meira Magalhães
YR 2015
UL http://bmjopen.bmj.com/content/5/4/e006048.abstract
AB Objective A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated.Design, setting and participants 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.Trial registration number Local Ethics Committee (licence 150/2009).