Incidence of HFE Gene Mutations in Chinese Patients with Myelodysplastic Syndrome and Aplastic Anemia

The C282Y and H63D mutations of HFE gene responsible for hereditary hemochromatosis lead to absorption of excess dietary iron, tissue iron deposition and occurrence of clinical complications such as congestive heart failure, arrhythmia, hepatocellular cirrhosis, insulin resistance and diabetes. Iron overload is one important clinical feature in patients with myelodysplastic syndrome (MDS) and aplastic anemia(AA). However, the conflict has been existing about influence of HFE gene mutations on iron overload in MDS patients. In the present study, we analyzed the incidence of the C282Y and H63D mutations of HFE gene in 271 MDS patients, 402 AA patients and 1615 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No C282Y mutations and compound heterozygote were observed in the entire cohort. The genotype distribution of H63D heterozygous and homozygous did not differ significantly in AA cases from those in controls(9.7%vs. 10.2%, 0.25%vs. 0.24% respectively, Pearson Chi-square p both >0.05). While the frequency of the H63D heterozygous in MDS patients was significantly lower than controls (4.1%vs. 10.7%, Pearson Chi-square p=0.002). H63D homozygous was not found in MDS patients. The incidence of C282Y and H63D mutations of HFE gene in Chinese MDS cases is lower than those reported in the literature. Comparing the pretransfusion serum ferritin(SF), serum iron concentration(SI) and transferrin saturation values(TS) between HFE-mutation and HFE-wild MDS groups, we did not find a significant difference (all P>0.05); However, Only SI values were significantly higher in the HFE-mutation AA cases than those in HFE-wild ones[42.6(24.6–60.4)umol/Lvs. 32.0(8.4–63.3)umol/L, P=0.011]. We further estimated the function of important organs in MDS and AA patients. There is no significantly difference in Alanine amino transferase (ALT), Aspartate amino transferase (AST), fasting blood sugar, and electrocardiogram(ECG) between HFE-mutation and HFE-wild MDS and AA groups irrespective of the red blood cell transfusion history. The results suggest that the distribution of C282Y and H63D mutations has ethnic and genetic differences, and is very rare in Chinese population. The mutations of HFE gene are not main factors of iron overload in Chinese patients with myelodysplastic syndrome and aplastic anemia.