>Revista de Hematología
>Year 2012, Issue 2
Pandey S, Pandey S, Shah V, Mani MR, Seath T, Saxena R
H63D hereditary hemochromatosis and iron metabolism in Indian sickle cell patients
Rev Hematol Mex 2012; 13 (2)
PDF: 81.63 Kb.
Background: Hereditary hemochromatosis is an iron metabolism disorder characterized by increased iron absorption and storage. H63D mutation of HFE gene may be associated with iron overload in Indian sickle cell patients.
Objective: determine the prevalence of the H63D mutations and their effect on iron metabolism in Indian sickle cell patients.
Material and Method: Study subjects were sickle cell patients (50 sickle cell anemia and 67 sickle β -thalassemia). One hundred seventy, age and sex matched healthy controls were recruited to compare the frequency of H63D mutation. Complete blood count was measured by automated cell analyzer and quantitative assessment of hemoglobin was performed by high performance liquid chromatography. DNA was extracted from the peripheral blood leucocytes by phenol-chloroform method. HFE gene mutations H63D was determined by PCRRFLP and PCR products were digested with restriction enzymes Bcl-1. Iron studies were done by standard laboratory method. Statistical analysis was performed on EpiInfo statistics software. Yates’ chi-square test was used to assess inter-group significance and t- test used to compares the means of two groups on GraphPad software.
Result: The prevalence of HFE mutation H63D was investigated among 50 sickle cell anemia and 67 sickle β-thalassemia patients. The prevalence of H63D was statistically significant in the group (p-value, ± 0.004 and ± 0.057). Serum iron in the H63D group were higher in comparison to without H63D group of patients (p-value ‹001).
Conclusion: H63D mutation present significantly and associated with increased iron absorption and low iron metabolism in Indian sickle cell patients.
||HFE, SCD, H63D, Hemochromatosis.
Gabutti V, Piga A. Results of long-term iron-chelating therapy. Acta Haematol 1996; 95:26-36.
Griffiths W, Cox T. Haemochromatosis: novel gene discovery and the molecular pathophysiology of iron metabolism. Hum Mol Genet 2000; 9: 2377-2382.
Hash RB. Hereditary hemochromatosis. J Am Board Fam Pract 2001; 14: 266-273.
Swinkels DW, Janssen MC, Bergmans J, Marx JJ. Hereditary hemochromatosis: genetic complexity and new diagnostic approaches. Clin Chem 2006; 52: 950-968.
Barton JC, Shih WW, Sawada-Hirai R, Acton RT, Harmon L, Rivers C, Rothenberg BE. Genetic and clinical description of hemochromatosis probands and heterozygotes: evidence that multiple genes linked to the major histocompatibility complex are responsible for hemochromatosis. Blood Cells Mol Dis 1997; 23: 135-145.
Beutler E. The significance of the 187G (H63D) mutation in hemochromatosis. Am J Hum Genet 1997; 61: 762-764.
Mura C, Raguenes O, Ferec C. HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood 1999; 93: 2502-2505.
Agostinho MF, Arruda VR, Basseres DS, et al. Mutation analysis of the HFE gene in Brazilian populations. Blood Cells Mol Dis 1999; 25(5-6):324-327.
Calado RT, Franco RF, Pazin-Filho A, Simões MV, Marin-Neto JA, Zago MA. HFE gene mutations in coronary atherothrombotic disease. Braz J Med Biol Res 2000; 33(3):301-306.
Garewal G, Das R, Kaur J, Chawla Y. H63D mutation of the Hfe gene in beta thalassemia traits does not cause iron overload and hereditary haemochromatosis in North India is of the Non-Hfe Type. Blood 2002; Abstract No. 3465, 100 (11): 4b.
Garewal G, Das R, Ahluwalia J, Marwaha RK. Prevalence of the H63D mutation of the HFE in north India: its presence does not cause iron overload in beta thalassemia trait. Eur J Haematol 2005; 74: 333-336.
Thakur V, Guptan RC, Hashmi AZ, Sakhuja P, Malhotra V, Sarin SK. Absence of hemochromatosis associated Cys282Tyr HFE gene mutation and low frequency of hemochromatosis phenotype in nonalcoholic chronic liver disease patients in India. J Gastroenterol Hepatol 2004; 19: 86-90.
Shukla P, Julka S, Bhatia E, Shah S, Nagral A, Aggarwal R. HFE, hepcidin and ferroportin gene mutations are not present in Indian patients with primary haemochromatosis. Natl Med J India 2006; 19: 20-23.
Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996; 13: 399-408.
Fleming DJ, Jacques PF, Tucker KL, et al. Iron status of the free-living, elderly Framingham Heart Study cohort: an ironreplete population with a high prevalence of elevated iron stores. Am J Clin Nutr 2001; 73(3):638-646.
Brissot P. Hemochromatosis at the intersection of classical medicine and molecular biology. C R Acad Sci III 2001; 324: 795-804.
Jazayeri M, Bakayev V, Adibi P, Haghighi RF, Zakeri H, Kalantar E, et al. Frequency of HFE gene mutations in Iranian betathalassaemia minor patients. Eur J Haematol 2003; 71: 408-411.
Alexander J, Kowdley KV. Hereditary hemochromatosis: genetics, pathogenesis, and clinical management. Ann Hepatol 2005; 4: 240-247.
Martins R, Picanco I, Fonseca A, Ferreira L, Rodrigues O, Coelho M, et al. The role of HFE mutations on iron metabolism in betathalassemia carriers. J Hum Genet 2004; 49: 651-55.
Chan V, Wong MS, Ooi C, Chen FE, Chim CS, Liang RH, et al. Can defects in transferrin receptor 2 and hereditary hemochromatosis genes account for iron overload in HbH disease? Blood Cells Mol Dis 2003; 30:107-111.
Powell LW. Hereditary hemochromatosis and iron overload diseases. J Gastroenterol Hepatol 2002; 17:191-195.
Camaschella C, Piperno A. Hereditary hemochromatosis: recent advances in molecular genetics and clinical management. Haematologica 1997; 82(1):77-84.
Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999; 341(10):718-724.
Steinberg KK, Cogswell ME, Chang JC, et al. Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States. JAMA 2001; 285(17):2216-2222.
>Revista de Hematología
>Year 2012, Issue 2