Putative role of Bach1 gene in HbE/beta-thalassaemia patients

Beta thalassaemia is an autosomal blood disorder due to a quantitative reduction or total absence of beta globin chain synthesis caused by beta globin gene mutations. Haemoglobin E/ beta thalassaemia individuals have a diverse clinical severity due to globin chain imbalance and the effects of other...

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Main Author:	Lee, Tze Yan
Format:	Thesis
Language:	English
Published:	2013
Subjects:	BACH1 protein human beta-Thalassemia - Genetics beta-Thalassemia - Blood
Online Access:	http://psasir.upm.edu.my/id/eprint/75309/1/FPSK%28M%29%202013%2047%20IR.pdf
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spelling	my-upm-ir.753092019-11-21T08:02:32Z Putative role of Bach1 gene in HbE/beta-thalassaemia patients 2013-07 Lee, Tze Yan Beta thalassaemia is an autosomal blood disorder due to a quantitative reduction or total absence of beta globin chain synthesis caused by beta globin gene mutations. Haemoglobin E/ beta thalassaemia individuals have a diverse clinical severity due to globin chain imbalance and the effects of other modifiers. Basic leucine zipper transcription factor 1 (Bach1) is known to be among the crucial molecules that has the ability to regulate gene expression when faced with oxidative stress. This study was done to investigate the role of Bach1 gene in HbE/ beta thalassaemia patients. Peripheral blood samples from 62 patients were collected. Full blood count analysis and HPLC were performed on the peripheral blood. Patients with blood transfusions of less than three months were excluded. A total of 47 selected samples without underlying iron deficiency or alpha thalassaemia co-inheritance were genotyped with ARMS PCR for common beta globin mutations and detection of uncommon beta globin mutations were done via direct gene sequencing. TaqMan® quantitative RT-PCR was employed to correlate Bach1 expression to severity, HO-1 and globin expression levels of HbE/ beta thalassaemia. Bach1 expression among 47 HbE/ beta thalassaemia patients varied up to 2-log differences which was positively correlated to age (p=0.006), alpha globin expression level (p=0.002), beta globin expression level (p=0.001), gamma globin expression level (p=0.001) and HO-1 expression level (p=0.001). Apart from that, Bach1 expression was also negatively correlated to reticulocytes level (p=0.005). The positive correlation of Bach1 expression with age could be due to the increasing oxidative stress caused by natural cellular ageing process. Excess precipitated alpha chains and unstable beta globin chains cause Bach1 expression to increase whereas Bach1 is correlated indirectly with gamma globin chains to ameliorate the clinical severity of HbE/ beta thalassaemia. The compensatory mechanism of Bach1 trying to counter-react with the increased reticulocyte counts and the indirect link of Bach1 with HO-1 as a cytoprotective vehicle further substantiate the role of Bach1 in modifying the phenotypic severity in HbE/ beta thalassaemia. Taken together, these results suggest that Bach1 could be a potential modifier of HbE/ beta thalasssaemia individuals. BACH1 protein, human beta-Thalassemia - Genetics beta-Thalassemia - Blood 2013-07 Thesis http://psasir.upm.edu.my/id/eprint/75309/ http://psasir.upm.edu.my/id/eprint/75309/1/FPSK%28M%29%202013%2047%20IR.pdf text en public masters Universiti Putra Malaysia BACH1 protein, human beta-Thalassemia - Genetics beta-Thalassemia - Blood
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	BACH1 protein human beta-Thalassemia - Genetics beta-Thalassemia - Blood
spellingShingle	BACH1 protein human beta-Thalassemia - Genetics beta-Thalassemia - Blood Lee, Tze Yan Putative role of Bach1 gene in HbE/beta-thalassaemia patients
description	Beta thalassaemia is an autosomal blood disorder due to a quantitative reduction or total absence of beta globin chain synthesis caused by beta globin gene mutations. Haemoglobin E/ beta thalassaemia individuals have a diverse clinical severity due to globin chain imbalance and the effects of other modifiers. Basic leucine zipper transcription factor 1 (Bach1) is known to be among the crucial molecules that has the ability to regulate gene expression when faced with oxidative stress. This study was done to investigate the role of Bach1 gene in HbE/ beta thalassaemia patients. Peripheral blood samples from 62 patients were collected. Full blood count analysis and HPLC were performed on the peripheral blood. Patients with blood transfusions of less than three months were excluded. A total of 47 selected samples without underlying iron deficiency or alpha thalassaemia co-inheritance were genotyped with ARMS PCR for common beta globin mutations and detection of uncommon beta globin mutations were done via direct gene sequencing. TaqMan® quantitative RT-PCR was employed to correlate Bach1 expression to severity, HO-1 and globin expression levels of HbE/ beta thalassaemia. Bach1 expression among 47 HbE/ beta thalassaemia patients varied up to 2-log differences which was positively correlated to age (p=0.006), alpha globin expression level (p=0.002), beta globin expression level (p=0.001), gamma globin expression level (p=0.001) and HO-1 expression level (p=0.001). Apart from that, Bach1 expression was also negatively correlated to reticulocytes level (p=0.005). The positive correlation of Bach1 expression with age could be due to the increasing oxidative stress caused by natural cellular ageing process. Excess precipitated alpha chains and unstable beta globin chains cause Bach1 expression to increase whereas Bach1 is correlated indirectly with gamma globin chains to ameliorate the clinical severity of HbE/ beta thalassaemia. The compensatory mechanism of Bach1 trying to counter-react with the increased reticulocyte counts and the indirect link of Bach1 with HO-1 as a cytoprotective vehicle further substantiate the role of Bach1 in modifying the phenotypic severity in HbE/ beta thalassaemia. Taken together, these results suggest that Bach1 could be a potential modifier of HbE/ beta thalasssaemia individuals.
format	Thesis
qualification_level	Master's degree
author	Lee, Tze Yan
author_facet	Lee, Tze Yan
author_sort	Lee, Tze Yan
title	Putative role of Bach1 gene in HbE/beta-thalassaemia patients
title_short	Putative role of Bach1 gene in HbE/beta-thalassaemia patients
title_full	Putative role of Bach1 gene in HbE/beta-thalassaemia patients
title_fullStr	Putative role of Bach1 gene in HbE/beta-thalassaemia patients
title_full_unstemmed	Putative role of Bach1 gene in HbE/beta-thalassaemia patients
title_sort	putative role of bach1 gene in hbe/beta-thalassaemia patients
granting_institution	Universiti Putra Malaysia
publishDate	2013
url	http://psasir.upm.edu.my/id/eprint/75309/1/FPSK%28M%29%202013%2047%20IR.pdf
_version_	1747813028543332352

Putative role of Bach1 gene in HbE/beta-thalassaemia patients

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