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

ObjectiveA relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated.Design, setting and participantsAn 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.MethodsIOL 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.ResultsThe 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.ConclusionsWe 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 numberLocal Ethics Committee (licence 150/2009).

Could haemochromatosis (HFE) gene mutations affect response to iron chelation in myelodysplastic syndrome? – Response to Lucijanic and Kusec

“…The frequency of HFE SNVs in our patient cohort was as previously reported in the literature (Marchall et al , ; De Souza et al , ; Lee et al , ). In particular, the frequency of the H63D variant was 22·7% (10 out of 44 patients), whereas it was 4·5% (2 out of 44 patients) for both S65C and C282Y SNVs.…”

“…The authors reported that neither patients' characteristics (including baseline and follow-up ferritin concentrations), nor mutations in any of the specific genes frequently mutated in myeloid malignancies showed significant associations with the occurrence of HI during ICT. We would like to point out that haemochromatosis (HFE) gene mutations, which affect significant proportion of MDS patients and increase the risk of iron accumulation in this context (De Souza et al, 2015;Lucijanic et al, 2016), were not assessed by Fabiani et al (2019).…”

“…HFE polymorphisms are relatively common in Caucasians. The frequency of the major HFE polymorphism, H63D variant is around 22–28%, whereas those of S65C and C282Y are lower (6–10%) (Marchall et al , ; De Souza et al , ; Lee et al , ).…”

Beyond Human Leukocyte Antigen Class I Antigens: Hereditary Hemochromatosis Gene Mutations in Recurrent Aphthous Oral Ulcers and Behçet Disease in the South of Tunisia

“…Based on stratification to clinical manifestations, the isolated RAOU was negatively associated with HLA-A1 with a difference close to significance (12 [14.81%] vs. 32 [26.02%] in HCs; p = 0.06). Furthermore, patients with mucocutaneous features had a higher frequency of HLA-B51 (14, 24.14%) than patients without mucocutaneous involvement (11,11.37%). Considering HFE mutations, patients with isolated RAOU had a higher frequency of H63D when compared with other subgroups, especially after limiting the comparison to 27 patients of at least 5 years of followup.…”

“…The HFE mutation is encountered in hereditary hemochromatosis [6] . It is also implicated in other diseases, such as neoplasia [8][9][10] and myelodysplastic syndromes [11] . Its association with RAOU or BD has not yet been described.…”