β-thalassemia comprises a group of heterogeneous autosomal recessive hereditary anemias characterized by the reduction or absence of β-globin chain synthesis, and it is a highly prevalent disease affecting 1.5% of the global population. Three different clinical conditions are recognized in patients with β-thalassemia minor (trait) being the asymptomatic form, β-thalassemia major (TM) being the most severe form of the disease and β-thalassemia intermedia (TI) presenting with variable severity. Despite extensive characterization of the genetic basis of disease pathogenesis, currently the classification of patients relies on the severity of symptoms and HbF levels regardless of the underlying genotype. Thus, the aim of the study was to develop an approach for patient stratification based on gene expression, pinpoint the targets that dictate each phenotype and provide a framework for the development of therapeutic strategies focused on these targets. To this end, we have analysed the gene expression profiles of TI, TM and healthy individuals using RNA-seq (NCBI, GSE117221) and we have studied the differentially expressed genes (DEGs) and pathways irrespective to patient genotype. Interestingly, after analysis of various confounding factors, we identified gender differences in the patients’ expression profiles suggesting that males and females are differentially affected by β-thalassemia. Thus, taking gender into account might benefit prognosis, diagnosis, stratification and therapeutic management of the disease.

Sex-specific transcriptional profiles identified in β-thalassemia patients

Bianchi, Nicoletta;Cosenza, Lucia Carmela;Zuccato, Cristina;Gambari, Roberto;
2021

Abstract

β-thalassemia comprises a group of heterogeneous autosomal recessive hereditary anemias characterized by the reduction or absence of β-globin chain synthesis, and it is a highly prevalent disease affecting 1.5% of the global population. Three different clinical conditions are recognized in patients with β-thalassemia minor (trait) being the asymptomatic form, β-thalassemia major (TM) being the most severe form of the disease and β-thalassemia intermedia (TI) presenting with variable severity. Despite extensive characterization of the genetic basis of disease pathogenesis, currently the classification of patients relies on the severity of symptoms and HbF levels regardless of the underlying genotype. Thus, the aim of the study was to develop an approach for patient stratification based on gene expression, pinpoint the targets that dictate each phenotype and provide a framework for the development of therapeutic strategies focused on these targets. To this end, we have analysed the gene expression profiles of TI, TM and healthy individuals using RNA-seq (NCBI, GSE117221) and we have studied the differentially expressed genes (DEGs) and pathways irrespective to patient genotype. Interestingly, after analysis of various confounding factors, we identified gender differences in the patients’ expression profiles suggesting that males and females are differentially affected by β-thalassemia. Thus, taking gender into account might benefit prognosis, diagnosis, stratification and therapeutic management of the disease.
2021
Nanou, Aikaterini; Toumpeki, Chrisavgi; Fanis, Pavlos; Bianchi, Nicoletta; Cosenza, Lucia Carmela; Zuccato, Cristina; Sentis, George; Giagkas, Giorgos; Stephanou, Coralea; Phylactides, Marios; Christou, Soteroula; Hadjigavriel, Michalis; Sitarou, Maria; Lederer, Carsten W; Gambari, Roberto; Kleanthous, Marina; Katsantoni, Eleni
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2426242
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