Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Genetic Modifiers of Hemoglobinopathies: Recent Advances and Future Directions
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Genetic Modifiers of Hemoglobinopathies: Recent Advances and Future Directions

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 3678

Special Issue Editors

Prof. Dr. Alex Felice

E-Mail Website
Guest Editor
Centre for Molecular Medicine and Biobanking, L-Università ta' Malta, Msida 2080, Malta
Interests: human hemoglobinopathies and globin gene control; human genomics
Dr. Petros Kountouris

E-Mail Website
Guest Editor
Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus
Interests: hemoglobinopathies; genetic modifiers; patient registries; biological databases
Dr. Carsten W. Lederer

E-Mail Website1 Website2
Guest Editor
Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus
Interests: advanced therapies; genetic modifiers; regulation of globin expression; rare anemias
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hemoglobinopathies, including sickle cell disease and thalassemia syndromes, are the most common monogenic diseases worldwide. Although their primary cause is well established through known pathogenic variants in the two globin gene clusters, the diverse clinical manifestations and the varying severity of hemoglobinopathies are largely attributed to the influence of genetic modifiers. Hundreds of genetic modifiers of different hemoglobinopathy phenotypes have already been identified by association studies, and genome-wide association studies (GWAS) in particular have proven to be powerful tools for the evaluation of the effect of genetic loci on specific disease phenotypes. Established modifiers serve as therapeutic targets, and have already greatly contributed to existing insights in the molecular mechanisms of disease pathogenicity. However, it is expected that there are many additional genetic variants that can modify disease severity and response to treatment. Taken together, a comprehensive understanding of modifiers is critical, as they will increasingly inform genetic counselling, diagnosis, prognosis, treatment decisions and therapy development for hemoglobinopathies.

The International Hemoglobinopathy Research Network (INHERENT; https://inherentnetwork.org) was recently established to study the role of genetic modifiers in hemoglobinopathies, through a large-scale, multi-ethnic GWAS. INHERENT brings together nine existing international or regional consortia in the field of hemoglobinopathies, and involves more than 200 experts from over 110 organizations, spanning 44 countries worldwide. With a target sample size of 30,000 patients and by promoting the participation of different populations, INHERENT aims to address challenges of previous studies related to small sample sizes, low statistical power and limited genetic diversity.

For this Special Issue, we aim to compile current knowledge and identify gaps related to the role of genetic modifiers for hemoglobinopathies and to highlight key priority areas for future collaborative research through INHERENT.

We welcome original research articles, reviews, opinion papers, perspectives, and short communications on topics related to the role of genetic modifiers and associated phenotypes in hemoglobinopathies and encourage the inclusion of illustrations of concepts and pathways.

Prof. Dr. Alex Felice
Dr. Petros Kountouris
Dr. Carsten W. Lederer
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hemoglobinopathies
  • genetic modifiers
  • thalassemia
  • sickle cell disease
  • association studies
  • biomarkers
  • GWAS

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Review

17 pages, 879 KiB  
Review
Pulmonary Hypertension in Sickle Cell Disease: Novel Findings of Gene Polymorphisms Related to Pathophysiology
by Sevastianos Chatzidavid, Pagona Flevari, Ioanna Tombrou, Georgios Anastasiadis and Maria Dimopoulou On behalf of the International Hemoglobinopathy Research Network (INHERENT)
Int. J. Mol. Sci. 2024, 25(9), 4792; https://doi.org/10.3390/ijms25094792 (registering DOI) - 27 Apr 2024
Viewed by 94
Abstract
Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6–10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity [...] Read more.
Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6–10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-β) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients. Full article
(This article belongs to the Special Issue Genetic Modifiers of Hemoglobinopathies: Recent Advances and Future Directions)
26 pages, 3200 KiB  
Review
Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications
by Roberto Gambari, Aliyu Dahiru Waziri, Hemali Goonasekera and Emmanuel Peprah
Int. J. Mol. Sci. 2024, 25(8), 4263; https://doi.org/10.3390/ijms25084263 - 12 Apr 2024
Viewed by 566
Abstract
In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the [...] Read more.
In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the appropriate drug and the correct dosage for each patient. We first discussed the search for DNA polymorphisms associated with a high expression of γ-globin genes and identified this using GWAS studies and CRISPR-based gene editing approaches. We then presented validated DNA polymorphisms associated with a high HbF production (including, but not limited to the HBG2 XmnI polymorphism and those related to the BCL11A, MYB, KLF-1, and LYAR genes). The expression of microRNAs involved in the regulation of γ-globin genes was also presented in the context of pharmacomiRNomics. Then, the pharmacogenomics of validated fetal hemoglobin inducers (hydroxyurea, butyrate and butyrate analogues, thalidomide, and sirolimus), of iron chelators, and of analgesics in the pain management of SCD patients were considered. Finally, we discuss current clinical trials, as well as international research networks focusing on clinical issues related to pharmacogenomics in hematological diseases. Full article
(This article belongs to the Special Issue Genetic Modifiers of Hemoglobinopathies: Recent Advances and Future Directions)
►▼ Show Figures

Figure 1

18 pages, 1399 KiB  
Review
Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management
by Joanne Traeger-Synodinos, Christina Vrettou, Christalena Sofocleous, Matteo Zurlo, Alessia Finotti and Roberto Gambari
Int. J. Mol. Sci. 2024, 25(6), 3400; https://doi.org/10.3390/ijms25063400 - 17 Mar 2024
Viewed by 625
Abstract
In this short review, we presented and discussed studies on the expression of globin genes in β-thalassemia, focusing on the impact of α-globin gene expression and α-globin modifiers on the phenotype and clinical severity of β-thalassemia. We first discussed the impact of the [...] Read more.
In this short review, we presented and discussed studies on the expression of globin genes in β-thalassemia, focusing on the impact of α-globin gene expression and α-globin modifiers on the phenotype and clinical severity of β-thalassemia. We first discussed the impact of the excess of free α-globin on the phenotype of β-thalassemia. We then reviewed studies focusing on the expression of α-globin-stabilizing protein (AHSP), as a potential strategy of counteracting the effects of the excess of free α-globin on erythroid cells. Alternative processes controlling α-globin excess were also considered, including the activation of autophagy by β-thalassemia erythroid cells. Altogether, the studies reviewed herein are expected to have a potential impact on the management of patients with β-thalassemia and other hemoglobinopathies for which reduction in α-globin excess is clinically beneficial. Full article
(This article belongs to the Special Issue Genetic Modifiers of Hemoglobinopathies: Recent Advances and Future Directions)
►▼ Show Figures

Figure 1

17 pages, 612 KiB  
Review
Endocrinopathies in Hemoglobinopathies: What Is the Role of Iron?
by Paschalis Evangelidis, Theodora-Maria Venou, Barmpageorgopoulou Fani, Efthymia Vlachaki and Eleni Gavriilaki
Int. J. Mol. Sci. 2023, 24(22), 16263; https://doi.org/10.3390/ijms242216263 - 13 Nov 2023
Cited by 1 | Viewed by 1424
Abstract
Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ damage observed mainly in patients with β-thalassemia and rarely in SCD. Iron overload, oxidative stress-induced cellular damage, chronic anemia, and HCV infection contribute [...] Read more.
Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ damage observed mainly in patients with β-thalassemia and rarely in SCD. Iron overload, oxidative stress-induced cellular damage, chronic anemia, and HCV infection contribute to the development of endocrinopathies in β-thalassemia. The above factors, combined with vaso-occlusive events and microcirculation defects, are crucial for endocrine dysfunction in SCD patients. These endocrinopathies include diabetes mellitus, hypothyroidism, parathyroid dysfunction, gonadal and growth failure, osteoporosis, and adrenal insufficiency, affecting the quality of life of these patients. Thus, we aim to provide current knowledge and data about the epidemiology, pathogenesis, diagnosis, and management of endocrine disorders in β-thalassemia and SCD. We conducted a comprehensive review of the literature and examined the available data, mostly using the PubMed and Medline search engines for original articles. In the era of precision medicine, more studies investigating the potential role of genetic modifiers in the development of endocrinopathies in hemoglobinopathies are essential. Full article
(This article belongs to the Special Issue Genetic Modifiers of Hemoglobinopathies: Recent Advances and Future Directions)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop