Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Indian Journal of Hematology and Blood Transfusion
Published in: Indian Journal of Hematology and Blood Transfusion 4/2017

01-12-2017 | Original Article

The Effects of HFE Polymorphisms on Biochemical Parameters of Iron Status in Arab Beta-Thalassemia Patients

Authors: Suad AlFadhli, Matra Salem, D. K. Shome, Najat Mahdi, Rasheeba Nizam

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 4/2017

Login to get access

Abstract

In this study, the potential effect of three HFE gene polymorphisms (C282Y, H63D and S65C) and the SLC40A1 A77D polymorphism on iron balance was investigated in 234 subjects (91 Arab beta-thalassemia major (BTM) patients, 34 beta-thalassemia trait (BTT) individuals and 109 health controls). Genotyping was done using restriction-fragment-length polymorphism and direct-sequencing. Serum-iron, total iron binding capacity, transferrin and ferritin were estimated in all BTT and BTM, and in 65 healthy controls. H63D was the only polymorphism detected in our cohort. Allele frequency was 13% in both BTM and BTT and 10% in controls with no significant difference. Serum iron, ferritin and transferrin saturation were significantly higher in normal males heterozygous for H63D as compared to homozygous wild-type males. Ferritin was significantly higher in BTT males with or without H63D polymorphism when compared to the healthy males with H/H genotype. No such difference was observed between H/H versus H/D BTT subgroups. We conclude that H63D is the only significant hemochromatosis-associated polymorphism in the Arabian Gulf region. The heterozygous state of H63D may significantly alter iron parameters in normal males. In BTT, it appears that the beta-thalassemia allele has an overriding influence on ferritin values, and this generally manifest in males.
Literature
1.
Schranz M, Talasz H, Graziadei I et al (1999) Diagnosis of hepaticiron overload: a family study illustrating pitfalls in diagnosing hemochromatosis. Diagn Mol Pathol 18:53–60CrossRef
2.
Camaschella C (2005) Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 106:3710–3717CrossRefPubMed
3.
Gasparini P, Camaschella C (2004) Hereditary hemochromatosis: is the gene race over? Eur J Hum Genet 12:341–342CrossRefPubMed
4.
Parkkila S, Waheed A, Britton RS et al (1997) Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad Sci USA 94:13198–13202CrossRefPubMedPubMedCentral
5.
6.
7.
Pietrangelo A, Camaschella C (1998) Molecular genetics and control of iron metabolism in hemochromatosis. Haematologica 83:456–461PubMed
8.
9.
Feder JN, Gnirke A, Thomas W et al (1996) A novel MHC class i-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408CrossRefPubMed
10.
Waheed A, Parkkila S, Zhou XY et al (1997) Hereditary hemochromatosis: effects of C282Yand H63D mutations on association with b2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. Proc Natl Acad Sci USA 94:12384–12389CrossRefPubMedPubMedCentral
11.
Mura C, Raguenes O, Ferec C (1999) HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood 93:2502–2505PubMed
12.
Feder JN, Tsuchihashi Z, Irrinki A, Lee VK, Mapa FA, Morikang E et al (1997) The hemochromatosis founder mutation in HLA-H disrupts b2-microglobulin interaction and cell surface expression. J Biol Chem 272:14025–14028CrossRefPubMed
13.
Fleming RE, Britton RS (2006) Iron imports Vi. HFE and regulation of intestinal iron absorption. Am J Physiol Gastrointest Liver Physiol 290:G590–G594CrossRefPubMed
14.
Donovan A, Brownlie A, Zhou Y et al (2000) Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403:776–781CrossRefPubMed
15.
16.
Montosi G, Donovan A, Totaro A et al (2001) Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SlC11A3) gene. J Clin Invest 108:619–623CrossRefPubMedPubMedCentral
17.
Aguilar-Martinez P, Schved JF, Badens C et al (2000) Iron overload in thalassaemias and genetic haemochromatosis. Eur J Haematol 64:279–280CrossRefPubMed
18.
Borgna-Pignatti C, Solinas A, Bombieri C et al (1998) The haemochromatosis mutations do not modify the clinical picture of thalassaemia major in patients regularly transfused and chelated. Br J Haematol 103:813–816CrossRefPubMed
19.
Cappellini MD, Fargion SR, Sampietro M, Graziadei G, Fiorelli G (1998) Nontransfusional iron overload in thalassemia intermedia: role of the hemochromatosis allele. Blood 92:4479–4480PubMed
20.
Fargion SR, Sampietro M, Cappellini MD (2000) Thalassemia and their interactions with haemochromatosis. Cambridge University Press, Cambridge, pp 435–438
21.
Garewal G, Das R, Ahluwalia J, Marwaha RK (2005) 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 74:333–336CrossRefPubMed
22.
Yamsri S, Sanchaisuriya K, Fucharoen S et al (2007) H63D mutation of the hemochromatosis gene and serum ferritin levels in Thai thalassemia carriers. Acta Haematol 118:99–105CrossRefPubMed
23.
Fairbanks VF, Thibodeau SN, Granfortuna JM, Lubin IM, Silverman LM, Rohlfs EM (1997) Iron overloading in b-thalassemia trait and spherocytosis: analysis of C282Y and H63D mutations. Blood 190:abstr 2740
24.
Melis MA, Cau M, Deidda F, Barella S, Cao A, Galanello R (2002) H63D mutation in the HFE gene increases iron overload in beta-thalassemia carriers. Haematologica 87:242–245PubMed
25.
Ruiz-Arguelles GJ, Garces-Eisele J, Reyes-Nunez V et al (2001) Heterozygosity for the H63D mutation in the hereditary hemochromatosis (HFE) gene may lead into severe iron overload in beta-thalassemia minor: observations in a thalassemic kindred. Rev Invest Clin 53:117–120PubMed
26.
Politou M, Kalotychou V, Pissia M, Rombos Y, Sakellaropoulos N, Papanikolaou G (2004) The impact of the mutations of the HFE gene and of the SLC11A3 gene on iron overload in Greek thalassemia intermedia and beta(s)/beta (thal) anemia patients. Haematologica 89:490–492PubMed
27.
Agarwal S, Sankar VH, Tewari D, Pradhan M (2006) Ferroportin (SLC40A1) gene in thalassemic patients of indian descent. Clin Genet 70:86–87CrossRefPubMed
28.
29.
Alsmadi OA, Al-Kayal F, Al-Hamed M, Meyer BF (2006) Frequency of common HFE variants in the Saudi population: a high throughput molecular beacon-based study. BMC Med Genet 3:7–43
30.
Alkhateeb A, Uzrail A, Bodoor K (2009) Frequency of the hemochromatosis gene (HFE) variants in a Jordanian Arab population and in diabetics from the same region. Dis Markers 27:17–22CrossRefPubMedPubMedCentral
31.
Karimi M, Yavarian M, Delbini P, Harteveld CL, Farjadian S, Fiorelli G, Giordano PC (2004) Spectrum and haplotypes of the HFE hemochromatosis gene in Iran: H63D in beta-thalassemia major and the first E277K homozygous. Hematol J 5:524–527CrossRefPubMed
32.
de Diego C, Opazo S, Murga MJ, Martinez-Castro P (2007) H63D homozygotes with hyperferritinaemia: is this genotype, the primary cause of iron overload? Eur J Haematol 78:66–71CrossRefPubMed
33.
34.
Loria A, Konijn AM, Hershko C (1978) Serum ferritin in beta-thalassemia trait. Isr J Med Sci 14:1127–1131PubMed
35.
Da Fonseca SF, Kimura EY, Kerbauy J (1995) Assessment of iron status in individuals with heterozygotic beta-thalassemia. Rev Assoc Med Bras 41:203–206PubMed
Metadata
Title
The Effects of HFE Polymorphisms on Biochemical Parameters of Iron Status in Arab Beta-Thalassemia Patients
Authors
Suad AlFadhli
Matra Salem
D. K. Shome
Najat Mahdi
Rasheeba Nizam
Publication date
01-12-2017
Publisher
Springer India
Published in
Indian Journal of Hematology and Blood Transfusion / Issue 4/2017
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-016-0775-7

Other articles of this Issue 4/2017

Indian Journal of Hematology and Blood Transfusion 4/2017 Go to the issue

Correspondence

BCR-ABL and JAK2V617F Mutation Co-existence, Rare or Just Unexplored

Original Article

A Comparison Between MRIT2 and NT-ProBNP in Early Detection of Heart Diseases in Thalassemia Major Patients: A Cross-Sectional Study

Original Article

Percentage of Memory B Lymphocytes and Regulatory T Lymphocytes in Peripheral Blood are Low but Not Predictive of Therapy outcomes in Newly Diagnosed Adult Patients with Primary Immune Thrombocytopenia

Correspondence

CD138 Negative Plasma Cells in Relapsed CNS Multiple Myeloma

Short Communication

Validity of Estimation of Haemoglobin Content in Dried Blood Spot Samples

Original Article

The Impact of Transfusion and Chelation on Oxidative Stress in Immigrant Syrian Children with β-Thalassemia
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits