Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia

β-thalassaemia is a condition caused by the quantitative reduction or absence of β-globin chain synthesis due to β-globin gene mutations. It leads to excessive unpaired α-globin chains precipitates which causes membrane damage and ineffective erythropoiesis. Haemoglobin /β-thalassaemia patients have...

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Main Author:	Lim, Wai Feng
Format:	Thesis
Language:	English
Published:	2011
Subjects:	Thalassemia - blood Thalassemia - Diagnosis
Online Access:	http://psasir.upm.edu.my/id/eprint/21439/1/FPSK%28m%29_2011_22R.pdf
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id	my-upm-ir.21439
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spelling	my-upm-ir.214392022-01-26T04:39:45Z Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia 2011-04 Lim, Wai Feng β-thalassaemia is a condition caused by the quantitative reduction or absence of β-globin chain synthesis due to β-globin gene mutations. It leads to excessive unpaired α-globin chains precipitates which causes membrane damage and ineffective erythropoiesis. Haemoglobin /β-thalassaemia patients have a remarkable variability in clinical severity due to globin chain imbalance and effects of other modifiers. Alpha haemoglobin stabilizing protein (AHSP) is an abundant erythroid protein that binds specifically to free α-globin chains to prevent its precipitation. Studies suggest that partial or full knockdown of AHSP may exacerbate β-thalassaemia phenotype in humans. This study was done to investigate the association between AHSP and HbE/β-thalassaemia patients in Malaysia. Peripheral blood samples from 105 patients were collected. Full blood count analysis and HPLC were carried out on the peripheral blood. Patients with transfusions less than three months were excluded. In the end, 30 selected samples without underlying iron deficiency or co-inheritance of α-thalassaemia or extra α-genes were genotyped with ARMS PCR for common β-globin mutations and rare β-globin mutations were detected through sequencing. Common AHSP sequence variants were typed by tetra-primer ARMS PCR. TaqMan® quantitative RT-PCR was employed to correlate the AHSP expression to the severity and globin expression levels of HbE/β-thalassaemia. AHSP expression among 30 HbE/β-thalassaemia patients varied up to 4.50-log differences which was negatively correlated to MCH (p=0.009) and HbF (p=0.002), while positively correlated to alpha-globin expression level (p=0.003), betaglobin expression level (p=0.001) as well as excess alpha globins (p=0.004). The significant correlation between AHSP with MCH and HbF showed that AHSP increases when there are more unpaired α-globin chains. My study suggests that AHSP is a secondary compensatory mechanism to balance the excess α-globin chains in β-thalassaemia after the formation of HbF. This study further strengthens the theory that AHSP is a modifier for phenotypic severity in HbE/β-thalassaemia patients. Thalassemia - blood Thalassemia - Diagnosis 2011-04 Thesis http://psasir.upm.edu.my/id/eprint/21439/ http://psasir.upm.edu.my/id/eprint/21439/1/FPSK%28m%29_2011_22R.pdf application/pdf en public masters Universiti Putra Malaysia Thalassemia - blood Thalassemia - Diagnosis Faculty of Medicine and Health Sciences
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Thalassemia - blood Thalassemia - Diagnosis
spellingShingle	Thalassemia - blood Thalassemia - Diagnosis Lim, Wai Feng Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia
description	β-thalassaemia is a condition caused by the quantitative reduction or absence of β-globin chain synthesis due to β-globin gene mutations. It leads to excessive unpaired α-globin chains precipitates which causes membrane damage and ineffective erythropoiesis. Haemoglobin /β-thalassaemia patients have a remarkable variability in clinical severity due to globin chain imbalance and effects of other modifiers. Alpha haemoglobin stabilizing protein (AHSP) is an abundant erythroid protein that binds specifically to free α-globin chains to prevent its precipitation. Studies suggest that partial or full knockdown of AHSP may exacerbate β-thalassaemia phenotype in humans. This study was done to investigate the association between AHSP and HbE/β-thalassaemia patients in Malaysia. Peripheral blood samples from 105 patients were collected. Full blood count analysis and HPLC were carried out on the peripheral blood. Patients with transfusions less than three months were excluded. In the end, 30 selected samples without underlying iron deficiency or co-inheritance of α-thalassaemia or extra α-genes were genotyped with ARMS PCR for common β-globin mutations and rare β-globin mutations were detected through sequencing. Common AHSP sequence variants were typed by tetra-primer ARMS PCR. TaqMan® quantitative RT-PCR was employed to correlate the AHSP expression to the severity and globin expression levels of HbE/β-thalassaemia. AHSP expression among 30 HbE/β-thalassaemia patients varied up to 4.50-log differences which was negatively correlated to MCH (p=0.009) and HbF (p=0.002), while positively correlated to alpha-globin expression level (p=0.003), betaglobin expression level (p=0.001) as well as excess alpha globins (p=0.004). The significant correlation between AHSP with MCH and HbF showed that AHSP increases when there are more unpaired α-globin chains. My study suggests that AHSP is a secondary compensatory mechanism to balance the excess α-globin chains in β-thalassaemia after the formation of HbF. This study further strengthens the theory that AHSP is a modifier for phenotypic severity in HbE/β-thalassaemia patients.
format	Thesis
qualification_level	Master's degree
author	Lim, Wai Feng
author_facet	Lim, Wai Feng
author_sort	Lim, Wai Feng
title	Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia
title_short	Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia
title_full	Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia
title_fullStr	Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia
title_full_unstemmed	Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia
title_sort	association of alpha haemoglobin stabilizing protein in hbe/ beta-thalassaemia patients in malaysia
granting_institution	Universiti Putra Malaysia
granting_department	Faculty of Medicine and Health Sciences
publishDate	2011
url	http://psasir.upm.edu.my/id/eprint/21439/1/FPSK%28m%29_2011_22R.pdf
_version_	1747811492842962944

Association of Alpha Haemoglobin Stabilizing Protein in HbE/ Beta-Thalassaemia Patients in Malaysia

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