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HFE genotype and iron metabolism in Chinese patients with myelodysplastic syndromes and aplastic anemia

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Abstract

The incidence of HFE gene mutations in myelodysplastic syndrome (MDS) cases remains controversial. In this study, we examined the HFE C282Y and H63D mutations in 271 Chinese patients with MDS, 402 with aplastic anemia (AA) and 1,615 healthy controls by polymerase chain reaction–restriction fragment length polymorphism in combination with DNA sequencing. No C282Y mutations were observed in the entire cohort. The distribution of H63D heterozygous and homozygous genotypes was not significantly different between the AA cases and the controls (9.7% versus 10.2%, 0.25% versus 0.24%, respectively). While the H63D heterozygous genotype in MDS patients was significantly lower than that in the controls (4.1% versus 10.2%, p = 0.002), the H63D homozygous genotype was not detected in the MDS patients. The results suggest that HFE gene mutations are not common genetic factors in Chinese patients with MDS and AA. We also compared iron metabolic parameters, including serum ferritin, serum iron, and transferrin saturation values, between HFE mutant and HFE wild-type groups in the absence of transfusion iron overload, but no significant difference was found in either MDS or AA patients except that the level of serum iron in AA patients was significantly higher in mutant carriers than in those with wild-type HFE (p = 0.011). Similarly, there was no significant difference between HFE mutant and HFE wild-type MDS and AA patients in clinical indices such as alanine aminotransferase, aspartate aminotransferase, fasting blood sugar values, and electrocardiogram. The results suggest that H63D mutations may not have clinical significance in Chinese patients with MDS and AA.

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References

  1. Feder J, Gnirke A, Thomas W et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408

    Article  CAS  PubMed  Google Scholar 

  2. Nearman Z, Szpurka H, Serio B et al (2007) Hemochromatosis-associated gene mutations in atients with myelodysplastic syndromes with refractory anemia with ringed sideroblasts. Am J Hematol 82:1076–1079

    Article  CAS  PubMed  Google Scholar 

  3. Várkonyi J, Tarkovács G, Karádi I et al (2003) High incidence of hemochromatosis gene utations in the myelodysplastic syndrome: the Budapest Study on 50 patients. Acta Haematol 109:64–67

    Article  PubMed  Google Scholar 

  4. Dine G, Genty V, Rehn Y et al (2003) Iron overload MDS and HFE gene mutations: what relation? Leuk Res 27(S1):S122

    Google Scholar 

  5. Farquhar MJ, Bowen DT (2003) Oxidative stress and the myelodysplastic syndromes. Int J Hematol 77:342–350

    Article  CAS  PubMed  Google Scholar 

  6. Greenberg PL (2006) Myelodysplastic syndromes: iron overload consequences and current chelating therapies. J Natl Compr Canc Netw 4:91–96

    CAS  PubMed  Google Scholar 

  7. Leitch HA (2007) Improving clinical outcome in patients with myelodysplastic syndrome and iron overload using iron chelation therapy. Leuk Res 31(S3):S7–S9

    Article  CAS  PubMed  Google Scholar 

  8. Camitta BM, Thomas ED, Nathan DG et al (1979) A prospective study of androgens and bone marrow transplantation for treatment of severe aplastic anemia. Blood 53:504–514

    CAS  PubMed  Google Scholar 

  9. Milman N, Pedersen P, Ovesen L et al (2004) Frequency of the C282Y and H63D mutations of the hemochromatosis gene (HFE) in 2501 ethnic Danes. Ann Hematol 83:654–657

    Article  CAS  PubMed  Google Scholar 

  10. Mura C, Raguenes O, Férec C et al (1999) HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood 93:2502–2505

    CAS  PubMed  Google Scholar 

  11. Raddatz D, Legler T, Lynen R et al (2003) HFE genotype and parameters of iron metabolism in German first-time blood donors - evidence for an increased transferrin saturation in C282Y heterozygotes. Z Gastroenterol 41:1069–1076

    Article  CAS  PubMed  Google Scholar 

  12. Potekhina E, Lavrov A, Samokhodskaya L et al (2005) Unique genetic profile of hereditary hemochromatosis in Russians: high frequency of C282Y mutation in population, but not in patients. Blood Cells Mol Dis 35:182–188

    Article  CAS  PubMed  Google Scholar 

  13. Ruiz-Argüelles G, Garcés-Eisele J, Gelbart T et al (2000) Analysis of HFE-codon 63/282 (H63D/C282Y) gene variants in mexican mestizos. Blood donors and patients with hereditary hemochromatosis. Arch Med Res 31:422–424

    Article  PubMed  Google Scholar 

  14. Barton JC, Acton RT, Lovato L et al (2006) Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in Native Americans and whites in the Hemochromatosis and Iron Overload Screening Study. Clin Genet 69:48–57

    Article  CAS  PubMed  Google Scholar 

  15. Whitfield J, Cullen L, Jazwinska E et al (2000) Effects of HFE C282Y and H63D polymorphisms and polygenic background on iron stores in a large community sample of twins. Am J Hum Genet 66:1246–1258

    Article  CAS  PubMed  Google Scholar 

  16. Viprakasit V, Vathesathokit P, Chinchang W et al (2004) Prevalence of HFE mutations among the Thai population and correlation with iron loading in haemoglobin E disorder. Eur J Haematol 73:43–49

    Article  CAS  PubMed  Google Scholar 

  17. Dhillon BK, Das R, Garewal G et al (2007) Frequency of primary iron overload and HFE gene mutations (C282Y, H63D and S65C) in chronic liver disease patients in north India. World J Gastroenterol 13:2956–2959

    CAS  PubMed  Google Scholar 

  18. Lee S, Kim J, Shin S et al (2009) HFE gene mutations, serum ferritin level, transferrin saturation, and their clinical correlates in a Korean population. Dig Dis Sci 54:879–886

    Article  CAS  PubMed  Google Scholar 

  19. Sohda T, Yanai J, Soejima H et al (1999) Frequencies in the Japanese population of HFE gene mutations. Biochem Genet 37:63–68

    Article  CAS  PubMed  Google Scholar 

  20. Lin T, Lin C, Wang C et al (2005) Prevalence of HFE mutations and relation to serum iron status in patients with chronic hepatitis C and patients with nonalcoholic fatty liver disease in Taiwan. World J Gastroenterol 11:3905–3908

    CAS  PubMed  Google Scholar 

  21. Merryweather-Clarke A, Pointon J, Shearman J et al (1997) Global prevalence of putative haemochromatosis mutations. J Med Genet 34:275–278

    Article  CAS  PubMed  Google Scholar 

  22. Lin A, Yan W, Xu H et al (2007) Analysis of the HFE gene (C282Y, H63D and S65C) mutations in a general Chinese Han population. Tissue Antigens 70:252–255

    Article  CAS  PubMed  Google Scholar 

  23. Bennett JM (2000) World Health Organization classification of the acute leukemias and myelodysplastic syndrome. Int J Hematol 72:131–133

    CAS  PubMed  Google Scholar 

  24. Sassi R, Hmida S, Kaabi H et al (2004) Prevalence of C282Y and H63D mutations in the haemochromatosis (HFE) gene in Tunisian population. Ann Génét 47:325–330

    Article  CAS  PubMed  Google Scholar 

  25. Speletas M, Kioumi A, Mandala E et al (2003) Prevalence of hemochromatosis gene (HFE) mutations in Greek patients with myelodysplastic syndromes. Acta Haematol 110:53–54

    Article  PubMed  Google Scholar 

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Acknowledgements

This study is supported in part by the National Natural Science Funds (No. 30670899), Tianjin Key Natural Science Funds (No. 08JCZDJC19200), and National Key Technology R&D Program in China’s 11th Five-Year Plan (No. 2008BAI61B02).

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Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China

    Ling Nie, Lin Li, Lin Yang & Zhijian Xiao

  2. MDS Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China

    Yue Zhang & Zhijian Xiao

  3. MDS Centre, Institute of Hematology, Chinese Academy of Medical Sciences, 288 Nanjing Road, Tianjin, 300020, China

    Zhijian Xiao

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  1. Ling Nie
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  2. Lin Li
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  3. Lin Yang
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Correspondence to Zhijian Xiao.

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Nie, L., Li, L., Yang, L. et al. HFE genotype and iron metabolism in Chinese patients with myelodysplastic syndromes and aplastic anemia. Ann Hematol 89, 1249–1253 (2010). https://doi.org/10.1007/s00277-010-1016-z

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  • DOI: https://doi.org/10.1007/s00277-010-1016-z

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