Frequency of Hereditary Hemochromatosis (HFE) Gene Mutations in Egyptian Beta Thalassemia Patients and its Relation to Iron Overload

Azza Aboul Enein; Nermine A. El Dessouky; Khalda S. Mohamed; Shahira K. A. Botros; Mona F. Abd El Gawad; Mona Hamdy; Nehal Dyaa

doi:10.3889/oamjms.2016.055

Authors

Azza Aboul Enein Clinical Pathology Department, Kasr El Ainy Medical School, Cairo
Nermine A. El Dessouky Clinical Pathology Department, Kasr El Ainy Medical School, Cairo
Khalda S. Mohamed National Research Center, Cairo
Shahira K. A. Botros Clinical Pathology Department, Kasr El Ainy Medical School, Cairo
Mona F. Abd El Gawad National Research Center, Cairo
Mona Hamdy Pediatrics Department, Aboul Riche Pediatric Teaching Hospital, Cairo University, Cairo
Nehal Dyaa Aboul Riche Pediatric Teaching Hospital, Cairo University, Cairo

DOI:

https://doi.org/10.3889/oamjms.2016.055

Keywords:

Thalassemia, Iron overload, HFE, genes, PCR

Abstract

AIM: This study aimed to detect the most common HFE gene mutations (C282Y, H63D, and S56C) in Egyptian beta thalassemia major patients and its relation to their iron status.

SUBJECTS AND METHODS: The study included 50 beta thalassemia major patients and 30 age and sex matched healthy persons as a control group. Serum ferritin, serum iron and TIBC level were measured. Detection of the three HFE gene mutations (C282Y, H63D and S65C) was done by PCR-RFLP analysis. Confirmation of positive cases for the mutations was done by sequencing.

RESULTS: Neither homozygote nor carrier status for the C282Y or S65C alleles was found. The H63D heterozygous state was detected in 5/50 (10%) thalassemic patients and in 1/30 (3.3%) controls with no statistically significant difference between patients and control groups (p = 0.22). Significantly higher levels of the serum ferritin and serum iron in patients with this mutation (p = 001).

CONCLUSION: Our results suggest that there is an association between H63D mutation and the severity of iron overload in thalassemic patients.

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References

Fawdry AL. Erythroblastic anaemia of childhood (Cooley's anaemia) in Cyprus. Lancet. 1944;1:171â€“176. http://dx.doi.org/10.1016/S0140-6736(00)42998-3

Borgna-Pignatti C, Rugolotto S, De Stefano P. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004;89:1187â€“1193. PMid:15477202

Dhillon BK, Prakash S, Chandak GR, Chawla YK, Das R. H63D mutation in HFE gene is common in Indians and is associated with the European haplotype. J Genet. 2012;91(2):229-232. http://dx.doi.org/10.1007/s12041-012-0163-5 PMid:22942096

Oliveira TM, Souza FP, Jardim AC, Cordeiro JA, Pinho JR, Sitnik R. et al. HFE gene mutations in Brazilian thalassemic patients. Braz J Med Biol Res. 2006;39(12):1575-1580. http://dx.doi.org/10.1590/S0100-879X2006001200008 PMid:17160266

Sharma V, Panigrahi I, Dutta P, Tyagi S, Choudhry VP, Saxena R. HFE mutation H63D predicts risk of iron over load in thalassemia intermedia irrespective of blood transfusions. Indian J Pathol Microbiol. 2007;50(1):82-85. PMid:17474269

MoysÃ©s CB, Moreira ES, Asprino PF, GuimarÃ£es GS, Alberto FL. Simultaneous detection of the C282Y, H63D and S65C mutations in the hemochromatosis gene using quenched-FRET real-time PCR. Braz J Med Biol Res. 2008;41(10): 833-838. http://dx.doi.org/10.1590/S0100-879X2008001000001 PMid:19030706

Giardina PJ, Grady RW. Chelation therapy in beta-thalassemia: an optimistic update. Semin Hematol. 2001;38(4):360-366. http://dx.doi.org/10.1016/S0037-1963(01)90030-7

Jowkar Z, Geramizadeh B, Shariat M. Frequency of Two Common HFE Gene Mutations (C282Y and H63D) in a Group of Iranian Patients With Cryptogenic Cirrhosis. Hepat Mon. 2011;11(11):887-891. http://dx.doi.org/10.5812/kowsar.1735143X.3749 PMid:22308152 PMCid:PMC3269056

Camaschella C, Roetto A, De Gobbi M. Genetic haemochromatosis: genes and mutations associated with iron loading. Best Pract. Res. Clin. Haematol. 2002;15(2):261-276. http://dx.doi.org/10.1016/S1521-6926(02)90207-0

Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;201;21:5-11. http://dx.doi.org/10.1186/1750-1172-5-11

Karimi M, Yavarian M, Delbini P, Harteveld CL, Farjadian S, Fiorelli G, et al. Spectrum and haplotypes of the HFE hemochromatosis gene in Iran: H63D in beta-thalassemia major and the first E277K homozygous. Hematol J. 2004;5(6):524-527. http://dx.doi.org/10.1038/sj.thj.6200553 PMid:15570296

Mellouli F, El Borgi W, Kaabi H, Ben Hassen E, Sassi R, Hmida H, et al. HFE gene mutations in Tunisian major beta-Thalassemia and iron overload. Transfus Clin Biol. 2006;13(6):353-357. http://dx.doi.org/10.1016/j.tracli.2006.12.002 PMid:17303462

Kaur D, Andersen J. Does cellular iron dysregulation play a causative role in Parkinson's disease? Aging Res. Rev. 2004;3:327â€“334. http://dx.doi.org/10.1016/j.arr.2004.01.003 PMid:15231240

Melis MA, Cau M, Congiu R, Ruvoletto L, Cao A, Galanello R. Frequency of hemochromatosis C282Y and H63D mutations in Sardinia. Genet Test. 2002;6(4):327-329. http://dx.doi.org/10.1089/10906570260471886 PMid:12537659

Madani HA, Afify RA, Abd El-Aal AA, Salama N, Ramy N.2011 Distribution of C282Y and H Role of HFE gene mutations on developing iron overload in beta-thalassaemia carriers in Egypt. East Mediterr Health J. 2011;17(6):546-551. PMid:21796974

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(4):333-336. http://dx.doi.org/10.1111/j.1600-0609.2004.00390.x PMid:15777346

LÃ³pez-Escribano H, Ferragut JF, Parera MM, Guix P, Castro JA, Ramon MM, et al. Effect of co-inheritance of Î²-thalassemia and hemochromatosis mutations on iron overload. Hemoglobin. 2012;36(1):85-92. http://dx.doi.org/10.3109/03630269.2011.637148 PMid:22122796