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Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy
BACKGROUND: β Thalassemia is one of the most common groups of hereditary haemoglobinopathies. Affected people with thalassemia major are dependent on regular blood transfusion which on the long term leads to iron overload. Hepcidin is a peptide hormone and an important regulator of iron homeostasis,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140315/ https://www.ncbi.nlm.nih.gov/pubmed/32268883 http://dx.doi.org/10.1186/s12881-020-01011-3 |
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author | Zarghamian, Parinaz Azarkeivan, Azita Arabkhazaeli, Ali Mardani, Ahmad Shahabi, Majid |
author_facet | Zarghamian, Parinaz Azarkeivan, Azita Arabkhazaeli, Ali Mardani, Ahmad Shahabi, Majid |
author_sort | Zarghamian, Parinaz |
collection | PubMed |
description | BACKGROUND: β Thalassemia is one of the most common groups of hereditary haemoglobinopathies. Affected people with thalassemia major are dependent on regular blood transfusion which on the long term leads to iron overload. Hepcidin is a peptide hormone and an important regulator of iron homeostasis, especially in thalassemia. Expression of this hormone is influenced by polymorphisms within the hepcidin gene, HAMP. Several studies emphasized the role of single nucleotide polymorphisms (SNPs) located in the promoter region of the gene. This study aimed to analyze the association between three SNPs in promoter of HAMP, c.-582A > G, c.-443C > T, and c.-153C > T, with iron overload in β-thalassemia major patients. METHODS: A total of 102 samples from β thalassemia major patients were collected. Genomic DNA was extracted and segments of DNA encompassing rs10421768 and rs142126068 were sequenced. Statistical analysis was performed by SPSS Statistics 23 using independent t test and Fisher’s exact test. RESULTS: A total of 102 adult β-thalassemia major patients were genotyped for three SNPs in the promoter region of HAMP gene by PCR and direct sequencing. Most of the patients (71.3%) were iron overloaded (based on plasma ferritin > 1000 ng/ml) in spite of receiving regular iron-chelating therapy. Our analysis revealed a statistically significant difference between the level of cardiac iron accumulation and c.-582A > G variant (p = 0.02). For c.-443C > T statistical analysis was on the edge of the significant relationship between the minor allele and serum ferritin (p = 0.058). All samples were homozygous for allele C of c.-153C > T. CONCLUSIONS: Despite chelating therapy, iron overload is still one of the main complications of thalassemia. Our findings and others emphasize the role of hepcidin -582A > G polymorphism as a key component of iron homeostasis in these patients. |
format | Online Article Text |
id | pubmed-7140315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71403152020-04-11 Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy Zarghamian, Parinaz Azarkeivan, Azita Arabkhazaeli, Ali Mardani, Ahmad Shahabi, Majid BMC Med Genet Research Article BACKGROUND: β Thalassemia is one of the most common groups of hereditary haemoglobinopathies. Affected people with thalassemia major are dependent on regular blood transfusion which on the long term leads to iron overload. Hepcidin is a peptide hormone and an important regulator of iron homeostasis, especially in thalassemia. Expression of this hormone is influenced by polymorphisms within the hepcidin gene, HAMP. Several studies emphasized the role of single nucleotide polymorphisms (SNPs) located in the promoter region of the gene. This study aimed to analyze the association between three SNPs in promoter of HAMP, c.-582A > G, c.-443C > T, and c.-153C > T, with iron overload in β-thalassemia major patients. METHODS: A total of 102 samples from β thalassemia major patients were collected. Genomic DNA was extracted and segments of DNA encompassing rs10421768 and rs142126068 were sequenced. Statistical analysis was performed by SPSS Statistics 23 using independent t test and Fisher’s exact test. RESULTS: A total of 102 adult β-thalassemia major patients were genotyped for three SNPs in the promoter region of HAMP gene by PCR and direct sequencing. Most of the patients (71.3%) were iron overloaded (based on plasma ferritin > 1000 ng/ml) in spite of receiving regular iron-chelating therapy. Our analysis revealed a statistically significant difference between the level of cardiac iron accumulation and c.-582A > G variant (p = 0.02). For c.-443C > T statistical analysis was on the edge of the significant relationship between the minor allele and serum ferritin (p = 0.058). All samples were homozygous for allele C of c.-153C > T. CONCLUSIONS: Despite chelating therapy, iron overload is still one of the main complications of thalassemia. Our findings and others emphasize the role of hepcidin -582A > G polymorphism as a key component of iron homeostasis in these patients. BioMed Central 2020-04-08 /pmc/articles/PMC7140315/ /pubmed/32268883 http://dx.doi.org/10.1186/s12881-020-01011-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Zarghamian, Parinaz Azarkeivan, Azita Arabkhazaeli, Ali Mardani, Ahmad Shahabi, Majid Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy |
title | Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy |
title_full | Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy |
title_fullStr | Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy |
title_full_unstemmed | Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy |
title_short | Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy |
title_sort | hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140315/ https://www.ncbi.nlm.nih.gov/pubmed/32268883 http://dx.doi.org/10.1186/s12881-020-01011-3 |
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