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Updated: Jun 20, 2026
Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
[Study on HFE gene mutations in patients with myelodysplastic syndromes and aplastic anemia]
Ling Nie1, Xiao-Fei Ai, Yi-Zhou Zheng
1The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
Objective:
To detect the incidence of the HFE gene C282Y and H63D mutations in patients with myelodysplastic syndromes (MDS) and aplastic anemia (AA), and analyze the relationship of these mutations with iron metabolism, and organs impairment from iron overload.
Methods:
The incidence of the C282Y and H63D mutations in 271 MDS, 402 AA patients and 1615 normal subjects was measured by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combining with DNA sequencing. Iron metabolism parameters and iron overload indices were retrospectively compared between HFE gene mutation and unmutation groups in MDS and AA patients with no transfusion history.
Results:
No C282Y and C282Y/H63D compound mutation was detected in all the three groups. The incidence of H63D heterozygous and homozygous genotype did not significantly differ between AA cases and controls (9.7% vs 10.2%, 0.25% vs 0.24% respectively, both P > 0.05). The frequency of H63D heterozygous genotype in MDS patients was significantly lower than that in controls (4.1% vs 10.2%, P = 0.002). H63D homozygous was not found in MDS patients. In both MDS and AA patients with no RBC transfusion history, serum ferritin (SF), transferrin saturation value (TS), serum iron concentration (SI) were close to or higher than normal; and unsaturated iron-binding capacity (UIBC) value was significantly lower. There was no significant difference in SF, SI, TS values between HFE-mutation and -unmutation MDS patients. For AA patients, only the level of SI was significantly higher in HFE-mutant group than in -unmutation group [42.6 (24.6-60.4) micromol/L vs 32.0 (8.4-63.3) micromol/L, P = 0.011]. There was no significant difference in the values of liver enzyme, fasting blood sugar (FBS), abnormal electrocardiogram (ECG), peripheral blood indices between HFE-mutation and -unmutation MDS and AA groups (all P > 0.05).
Conclusion:
The distribution of C282Y and H63D mutations has ethnic and genetic disparity, the frequency in Chinese population is lower than that in Caucasian. It seems that MDS and AA patients are susceptible to iron overload, in the diseases itself and the mutations of HFE gene are not the major factor for iron overload in the patients.
Insights
The HFE gene C282Y and H63D mutations are uncommon in Chinese patients with myelodysplastic syndromes (MDS) and aplastic anemia (AA). These HFE gene mutations are not the primary cause of iron overload in MDS and AA patients.
Area of Science:
- Hematology
- Genetics
- Iron Metabolism
Background:
- Myelodysplastic syndromes (MDS) and aplastic anemia (AA) are hematological disorders.
- Iron overload is a common complication in MDS and AA.
- The HFE gene mutations (C282Y and H63D) are associated with hereditary hemochromatosis, a disorder of iron overload.
Purpose of the Study:
- To determine the incidence of HFE gene C282Y and H63D mutations in Chinese patients with MDS and AA.
- To investigate the association between HFE gene mutations and iron metabolism in MDS and AA patients.
- To assess the impact of HFE gene mutations on organ impairment due to iron overload.
Main Methods:
- Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were used to detect HFE gene mutations.
- Iron metabolism parameters and iron overload indices were compared between patients with and without HFE mutations.
- The study included 271 MDS patients, 402 AA patients, and 1615 healthy controls.
Main Results:
- No C282Y or compound C282Y/H63D mutations were found.
- The H63D mutation frequency did not differ significantly between AA patients and controls.
- H63D heterozygous genotype frequency was lower in MDS patients than in controls (4.1% vs 10.2%, P = 0.002).
- MDS and AA patients without transfusions showed elevated iron parameters (serum ferritin, transferrin saturation, serum iron) and lower unsaturated iron-binding capacity.
- No significant differences in iron parameters or organ impairment markers were observed between HFE-mutated and unmutated MDS patients.
- AA patients with HFE mutations showed higher serum iron levels compared to those without mutations (P = 0.011).
Conclusions:
- The prevalence of HFE gene mutations C282Y and H63D is low in the Chinese population, differing from Caucasian populations.
- MDS and AA patients exhibit a predisposition to iron overload, irrespective of HFE gene mutations.
- HFE gene mutations are not the primary drivers of iron overload in MDS and AA patients.
