Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity

Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) is a common inherited genetic disorder. It is responsible for approximately half of all severe betathalassaemia cases globally. In the state of Kelantan, 50.93% of thalassaemic patients have Hb E/β-thalassaemia, and most of the cases are commo...

Full description

Saved in:

Bibliographic Details
Main Author:	Alsaleh, Heba A. A.
Format:	Thesis
Language:	English
Published:	2022
Subjects:	RC Internal medicine
Online Access:	http://eprints.usm.my/57751/1/HEBA%20A.%20A.%20ALSALEH-FINAL%20THESIS%20P-UD001114%28R%29%20-24%20pages.pdf
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my-usm-ep.57751
record_format	uketd_dc
spelling	my-usm-ep.577512023-04-11T00:49:16Z Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity 2022-08 Alsaleh, Heba A. A. RC Internal medicine Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) is a common inherited genetic disorder. It is responsible for approximately half of all severe betathalassaemia cases globally. In the state of Kelantan, 50.93% of thalassaemic patients have Hb E/β-thalassaemia, and most of the cases are commonly seen in Malay compared to Chinese and Indian. Clinical heterogeneity is the most outstanding criteria among these patients ranging from mild to severe clinical courses that need a regular blood transfusion. There are many modifiers found to affect the disease presentation. However, the exact reasons behind this heterogeneity are not fully understood. This research aimed to study the differential gene expression and their possible role in the disease presentation and complications development in both transfusion-dependent (TDT) and non-transfusion dependent (NTDT) HbE/β-thalassaemia patients. It was conducted with the aid of RT2 profiler PCR array and microarray that were used in gene expressional study in reticulocytes and erythroid progenitors, respectively. Three normal controls and a total of 20 patients were enrolled in this study; 10 (50%) were TDT, and 10 (50%) NTDT. The reticulocytes study showed the up-regulation of BAX and BAD genes in TDT patients, which have a role in apoptosis induction through the mitochondrial apoptotic pathway. Their up-regulation in TDT may play a role in the reticulocytes’ apoptosis, mature RBCs' short life span and eryptosis. Flow cytometry study showed higher apoptosis in the erythroid progenitors of TDT patients. The increased apoptosis in erythroid progenitors and the up-regulation of BAD and BAX of reticulocytes in TDT may be linked to the down-regulation of the genes involved in the PI3k/AKT pathway in the same patients’ group genes. Pathway and ontology analysis showed the involvement of osteoporosis and bone regulating factors related to the VDR pathway and the negative regulation of osteoclast differentiation in the TDT group. The genes involved can be therapeutic targets like SPP1 and MAFB. Their activation act to reduce the disease burden by reducing anaemia and alleviating bone marrow complications. In summary, our study showed the expression of interesting genes and pathways that may potentially modify the disease presentation and the development of the complications. 2022-08 Thesis http://eprints.usm.my/57751/ http://eprints.usm.my/57751/1/HEBA%20A.%20A.%20ALSALEH-FINAL%20THESIS%20P-UD001114%28R%29%20-24%20pages.pdf application/pdf en public phd doctoral Universiti Sains Malaysia Pusat Pengajian Sains Pergigian
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	RC Internal medicine
spellingShingle	RC Internal medicine Alsaleh, Heba A. A. Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity
description	Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) is a common inherited genetic disorder. It is responsible for approximately half of all severe betathalassaemia cases globally. In the state of Kelantan, 50.93% of thalassaemic patients have Hb E/β-thalassaemia, and most of the cases are commonly seen in Malay compared to Chinese and Indian. Clinical heterogeneity is the most outstanding criteria among these patients ranging from mild to severe clinical courses that need a regular blood transfusion. There are many modifiers found to affect the disease presentation. However, the exact reasons behind this heterogeneity are not fully understood. This research aimed to study the differential gene expression and their possible role in the disease presentation and complications development in both transfusion-dependent (TDT) and non-transfusion dependent (NTDT) HbE/β-thalassaemia patients. It was conducted with the aid of RT2 profiler PCR array and microarray that were used in gene expressional study in reticulocytes and erythroid progenitors, respectively. Three normal controls and a total of 20 patients were enrolled in this study; 10 (50%) were TDT, and 10 (50%) NTDT. The reticulocytes study showed the up-regulation of BAX and BAD genes in TDT patients, which have a role in apoptosis induction through the mitochondrial apoptotic pathway. Their up-regulation in TDT may play a role in the reticulocytes’ apoptosis, mature RBCs' short life span and eryptosis. Flow cytometry study showed higher apoptosis in the erythroid progenitors of TDT patients. The increased apoptosis in erythroid progenitors and the up-regulation of BAD and BAX of reticulocytes in TDT may be linked to the down-regulation of the genes involved in the PI3k/AKT pathway in the same patients’ group genes. Pathway and ontology analysis showed the involvement of osteoporosis and bone regulating factors related to the VDR pathway and the negative regulation of osteoclast differentiation in the TDT group. The genes involved can be therapeutic targets like SPP1 and MAFB. Their activation act to reduce the disease burden by reducing anaemia and alleviating bone marrow complications. In summary, our study showed the expression of interesting genes and pathways that may potentially modify the disease presentation and the development of the complications.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Alsaleh, Heba A. A.
author_facet	Alsaleh, Heba A. A.
author_sort	Alsaleh, Heba A. A.
title	Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity
title_short	Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity
title_full	Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity
title_fullStr	Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity
title_full_unstemmed	Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity
title_sort	differential gene expression analyses in hbe/beta thalassaemia patients and their relationship to disease severity
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Pergigian
publishDate	2022
url	http://eprints.usm.my/57751/1/HEBA%20A.%20A.%20ALSALEH-FINAL%20THESIS%20P-UD001114%28R%29%20-24%20pages.pdf
_version_	1776101208399806464

Differential gene expression Analyses in HBE/BETA thalassaemia patients and their relationship to disease severity

Similar Items