Association of frequency of hereditary hemochromatosis (HFE)  gene mutations (H63D and C282Y) with iron overload in beta-thalassemia major patients in Pakistan

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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Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents

AIMS Molecular Science ◽

10.3934/molsci.2021018 ◽

2021 ◽

Vol 8 (4) ◽

pp. 233-247

Author(s):

Bhuvana Selvaraj ◽

◽

Sangeetha Soundararajan ◽

Shettu Narayanasamy ◽

Ganesan Subramanian ◽

...

Keyword(s):

Iron Overload ◽

Iron Status ◽

Globin Gene ◽

Hereditary Hemochromatosis ◽

Gene Mutations ◽

Autosomal Recessive Disorder ◽

Thalassemia Major ◽

Organ Damage ◽

Beta Thalassemia ◽

Hemochromatosis Gene

<abstract> <p>Hereditary Hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism associated with <italic>HFE</italic> gene mutations, characterized by increased iron absorption and accumulation leading to multi-organ damage caused by iron overload toxicity. Beta thalassemia is caused by a mutation in the human beta globin gene. Imbalanced production of globin chain results in beta thalassemia, where the unpaired alpha chains precipitates in red cell precursors leading to ineffective erythropoiesis and reduced RBC survival. Both HH and beta thalassemia condition results in rapid accumulation of iron lead to iron overload in tissues and organs. The study aims to analyze the frequency of <italic>HFE</italic> variants among beta thalassemia cases and their effect on iron overload. The frequency of three <italic>HFE</italic> variants C282Y, H63D, S65C was analyzed by PCR RFLP method among Beta Thalassemia Trait (BTT) (n = 203), Beta Thalassemia Major (BTM) (n = 19) and age and sex-matched control samples (n = 200). The present study furnished allele frequency of H63D variant in BTT, BTM and controls 8.13, 15.8 and 6% respectively. Ten out of 33 heterozygous H63D variants exhibited iron overload with higher ferritin levels indicating <italic>HFE</italic> variant might aggravate the absorption of iron. The C282Y variant was present in heterozygous state in 1 case among beta thalassemia carriers. The C282Y variant was absent among BTM and control cases. S65C <italic>HFE</italic> variant was absent in the present study. Iron overload was completely absent in the control cases among all three <italic>HFE</italic> genotypes. Hence it is inferred from the present investigation, analysis of <italic>HFE</italic> genes and iron status will remarkably help to reason out the probable reason behind the iron status and support in proper management of beta thalassemia cases.</p> </abstract>

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Hemochromatosis: one form of iron-overload diseases

Orvosi Hetilap ◽

10.1556/oh.2013.29668 ◽

2013 ◽

Vol 154 (29) ◽

pp. 1156-1164 ◽

Cited By ~ 3

Author(s):

Ferenc Szalay

Keyword(s):

Iron Overload ◽

Iron Metabolism ◽

Clinical Symptoms ◽

Fetal Liver ◽

Hereditary Hemochromatosis ◽

Gene Mutations ◽

Organ Injury ◽

Beta Thalassemia ◽

Hfe Gene ◽

Kinase Gene

Iron-overload diseases are typically insidious, causing progressive and irreversible organ injury before clinical symptoms develop. Some iron-overload diseases as HFE-associated hemochromatosis and beta-thalassemia are quite common, whereas others are very rare. Early diagnosis is important since iron toxicity can be attenuated or prevented. Significant progress of our knowledge on iron metabolism developed in the past years. We learned a lot about HFE gene mutations, function of ferroportin and hepcidin, the hypoferremia hormone produced by the liver. However, many questions are still open. Special forms of localized iron overload are the Hallervorden-Spatz syndrome and pantothenate kinase gene mutation associated neurodegeneration causing progressive extrapyramidal movement disorders. Neonatal hemochromatosis is a severe systemic iron-overload disorder due to gestational alloimmune liver disease caused by transplacental maternal IgG directed against the fetal liver. This review article gives an overview on iron metabolism and iron-overload disease. Pathomechanism, diagnosis and treatment of hereditary hemochromatosis are discussed. Orv. Hetil., 2013, 154, 1156–1164.

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Analysis of HFE gene mutations and HLA-A alleles in Brazilian patients with iron overload

Sao Paulo Medical Journal ◽

10.1590/s1516-31802006000200002 ◽

2006 ◽

Vol 124 (2) ◽

pp. 55-60 ◽

Cited By ~ 4

Author(s):

Rodolfo Delfini Cançado ◽

Aline Cristiane de Oliveira Guglielmi ◽

Carmen Silvia Vieitas Vergueiro ◽

Ernani Geraldo Rolim ◽

Maria Stella Figueiredo ◽

...

Keyword(s):

Iron Overload ◽

Binding Capacity ◽

Hereditary Hemochromatosis ◽

Gene Mutations ◽

Hfe Gene ◽

Outpatient Unit ◽

Laboratory Variables ◽

Hfe Gene Mutations ◽

Hfe Mutations ◽

Iron Binding Capacity

CONTEXT AND OBJECTIVE: Hemochromatosis is a common inherited disorder of iron metabolism and one of the most important causes of iron overload. The objective was to analyze the presence of C282Y, H63D and S65C mutations in the HFE gene and HLA-A alleles for a group of Brazilian patients with iron overload, and to correlate genotype with clinical and laboratory variables. DESIGN AND SETTING: Prospective study, in Discipline of Hematology and Oncology, Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo. METHODS: We studied 35 patients with iron overload seen at our outpatient unit between January 2001 and December 2003. Fasting levels of serum iron and ferritin, and total iron-binding capacity, were assayed using standard techniques. Determinations of C282Y, H63D and S65C mutations in the HFE gene and of HLA-A alleles were performed by polymerase chain reaction (PCR). RESULTS: Twenty-six out of 35 patients (74%) presented at least one of the HFE gene mutations analyzed. Among these, five (14%) were C282Y/C282Y, four (11%) C282Y/H63D, one (3%) H63D/H63D, six (17%) C282Y/WT and ten (29%) H63D/WT. No patients had the S65C mutation and nine (25%) did not present any of the three HFE mutations. Four out of five patients with C282Y/C282Y genotype (80%) and three out of four patients with C282Y/H63D genotype (75%) were HLA A*03. CONCLUSION: Analysis of HFE gene mutations constitutes an important procedure in identifying patients with hereditary hemochromatosis, particularly for patients with iron overload.

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