Hepcidin and HFE Polymorphisms and Ferritin Level in β-Thalassemia Major
Background: Thalassemia patients need repeated transfusion that lead to increased blood ferritin level and iron overload in the heart and liver. Because the roles of hepcidin antimicrobial peptide (HAMP) and hemocromatosis protein (HFE) in iron metabolism have been confirmed, this study investigated the effects of these gene's polymorphisms on blood ferritin levels and iron overload in the heart and liver in patients with beta thalassemia major
Materials and Methods: This cross-sectional study was conducted on 91 patients referring to the Hajar Hospital in Shahrekord, Iran in 2015. After the blood samples were collected, the ferritin levels were measured, DNA was extracted from the blood cells, and the types of polymorphisms were determined using PCR-RFLP. Data of MRI T2* in the heart and liver were drawn from the patients' medical files. Data analysis was conducted by t-test, chi-square test, Fisher's exact test, and Pearson correlation coefficient.
Results: There was no significant correlation between blood ferritin level and c.-582 A>G polymorphisms of hepcidin gene (p=0.58), and H63D of HFE gene (p=0.818). In addition, there was no significant association between the polymorphisms and heart and liver MRI, but there was a significant association between blood ferritin level and qualitative heart and liver MRI (r=-0.34, p=0.035 and r=-0.001, p=0.609, respectively).
Conclusion: In patients with β-thalassemia major, the presence of c.-582A>G HAMP and H63D HFE polymorphisms is not effective on blood ferritin level and iron overload in the heart and liver in the studied region.
Enein AA, El Dessouky NA, Mohamed KS, Botros SK, El Gawad MFA, Hamdy M, et al. Frequency of Hereditary Hemochromatosis (HFE) Gene Mutations in Egyptian Beta Thalassemia Patients and its Relation to Iron Overload. Open Access Maced J Med Sci. 2016;4(2):226-31.
Aboul-Enein A, Amal E-B, Hamdy M, Shaheen I, El-Saadany Z, Samir A, et al. Peripheral expression of hepcidin gene in Egyptian β-thalassemia major. Gene. 2015;564(2):206-9.
Walters G, Miller F, Worwood M. Serum ferritin concentration and iron stores in normal subjects. J. Clin. Pathol. 1973;26(10):770-2.
Pootrakul P, Vongsmasa V, La-Ongpanich P, Wasi P. Serum ferritin levels in β-thalassemi and the effect of splenectomy. Acta Haemat. 1981;66(4):244-250.
Lee SM, Loguinov A, Fleming RE, Vulpe CD. Effects of strain and age on hepatic gene expression profiles in murine models of HFE-associated hereditary hemochromatosis. Genes Nutr. 2015;10(1):1-9.
Melis MA, Cau M, Deidda F, Barella S, CaoA, Galanello R. H63D mutation in the HFE gene increases iron overload in beta-thalassemia carriers. Haematol Hematol J. 2002;87(3):242-5.
Turedi A, Oymak Y, Meşe T, Yaman Y, Bayraktaroglu S, Alpman A, et al. The effect of HFE polymorphisms on cardiac iron overload in patients with beta-thalassemia major. J Pediatr Hematol Oncol. 2013;30(8):755-60.
Brissot P, Guyader D, Loréal O, Lainé F, Guillygomarc'h A, Moirand R, et al. Clinical aspects of hemochromatosis. Transfus Sci. 2000;23(3):193-200.
Madani H, Afify R, El-Aal AA, Salama N, Ramy N. Role of HFE gene mutations on developing iron overload in Beta-thalassemia carriers in Egypt. East Mediterr Health J. 2011;17(6):546-551.
Zhang LQ, Liu H, Huang XF. Relation of JAGGED 1 and collagen type 1 alpha 1 polymorphisms with bone mineral density in Chinese postmenopausal women. Int J Clin Exp Pathol. 2014;7(10):7142-7147.
Bayele HK, Srai SK. Regulatory variation in hepcidin expression as a heritable quantitative trait. Biochem Biophys Res Commun. 2009;384(1):22-7.
Andreani M, Radio FC, Testi M, De Bernardo C, Troiano M, Majore S, et al. Association of hepcidin promoter c.-582 A>G variant and iron overload in thalassemia major. Haematol Hematol J. 2009;94(9):1293-6.
Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochim Biophys Acta. 2012;1823(9):1434-43.
López-Escribano H, Ferragut JF, Parera MM, Guix P, Castro JA, Ramon MM, et al. Effect of co-inheritance of β-thalassemia and hemochromatosis mutations on iron overload. Hemoglobin. 2012;36(1):85-92.
Garewal G, Das R, Ahluwalia J, Marwaha R. 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):333-6.
Mellouli F, El Borgi W, Kaabi H, Ben HE, Sassi R, Hmida H, et al. HFE gene mutations in Tunisian major beta-thalassemia and iron overload. Transfus Clin Biol. 2006;13(6):353-7.
Hanson E, Imperatore G, Burke W. HFE gene and hereditary hemochromatosis HuGE review. Am J Epidemiol. 2001;154(3):193-200.