Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan

Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder characterized by high cholesterol concentration which increases oxidative stress and leads to coronary artery disease. Mutation in exon 26 and exon 29 of Apolipoprotein B (APOB) gene is one of the causes of FH. Oxidized lo...

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Main Author:	Hamzan, Nur Suhana
Format:	Thesis
Language:	English
Published:	2016
Subjects:	Dissertations, Academic Preparation of theses Genetics
Online Access:	https://ir.uitm.edu.my/id/eprint/62287/1/62287.pdf
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spelling	my-uitm-ir.622872022-06-28T07:38:00Z Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan 2016-08 Hamzan, Nur Suhana Dissertations, Academic. Preparation of theses Genetics Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder characterized by high cholesterol concentration which increases oxidative stress and leads to coronary artery disease. Mutation in exon 26 and exon 29 of Apolipoprotein B (APOB) gene is one of the causes of FH. Oxidized low-density lipoprotein (oxLDL), F₂₋ isoprostanes (ISP) and Malondialdehyde (MDA) are established oxidative stress biomarker. The aim of this study is to investigate oxidative stress status and to identify genetic variants in APOB gene among FH patients and normocholesterolaemic (NC) subjects. Ninety-eight FH patients and 100 (age, gender and BMI matched) NC subjects were recruited in series of health screening programmes across the country. Fasting blood samples were analysed for serum oxLDL (ELISA), ISP (LCMS/MS) and MDA. Amplicons of exon 26 and 29 of APOB gene were screened by DNA sequencing. Ox-LDL, ISP and MDA concentrations were significantly higher in FH groups compared to NC (mean+SEM: 63.0+6.5 vs 25.5+1.2 (U/l), p<0.001); 749.7+74.0 vs 354.2+18.1 pg/ml, p<0.0001; 342.4+46.0 vs 162.7+13.5 nmol/g, p<0.0001). Ox-LDL shows significant correlation with glucose (p<0.05), TC (p<0.001), LDL-c (p<0.001) and HDL-c (p<0.01) in all subjects. High LDL-c was associated with high ox-LDL (p<0.001). LDL-c is an independent predictor for ox-LDL concentration (p<0.001). Known mutations were not found in all FH cases except for few insignificant genetic variations which are pThr2515Thr, p.Ile2716Ile, p.Pro2739Leu, p.Glu4181Lys, p.Arg4270Thr, p.Arg4297His and p.Ser4338Asn. These findings demonstrate that FH patients have higher oxidative stress concentration which suggests a greater risk of developing atherosclerosis. These results provide additional knowledge regarding FH in Malaysians. 2016-08 Thesis https://ir.uitm.edu.my/id/eprint/62287/ https://ir.uitm.edu.my/id/eprint/62287/1/62287.pdf text en public masters Universiti Teknologi MARA (Kampus Sg. Buloh) Faculty of Medicine Mohd Nawawi, Hapizah
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
advisor	Mohd Nawawi, Hapizah
topic	Dissertations, Academic Preparation of theses Genetics
spellingShingle	Dissertations, Academic Preparation of theses Genetics Hamzan, Nur Suhana Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan
description	Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder characterized by high cholesterol concentration which increases oxidative stress and leads to coronary artery disease. Mutation in exon 26 and exon 29 of Apolipoprotein B (APOB) gene is one of the causes of FH. Oxidized low-density lipoprotein (oxLDL), F₂₋ isoprostanes (ISP) and Malondialdehyde (MDA) are established oxidative stress biomarker. The aim of this study is to investigate oxidative stress status and to identify genetic variants in APOB gene among FH patients and normocholesterolaemic (NC) subjects. Ninety-eight FH patients and 100 (age, gender and BMI matched) NC subjects were recruited in series of health screening programmes across the country. Fasting blood samples were analysed for serum oxLDL (ELISA), ISP (LCMS/MS) and MDA. Amplicons of exon 26 and 29 of APOB gene were screened by DNA sequencing. Ox-LDL, ISP and MDA concentrations were significantly higher in FH groups compared to NC (mean+SEM: 63.0+6.5 vs 25.5+1.2 (U/l), p<0.001); 749.7+74.0 vs 354.2+18.1 pg/ml, p<0.0001; 342.4+46.0 vs 162.7+13.5 nmol/g, p<0.0001). Ox-LDL shows significant correlation with glucose (p<0.05), TC (p<0.001), LDL-c (p<0.001) and HDL-c (p<0.01) in all subjects. High LDL-c was associated with high ox-LDL (p<0.001). LDL-c is an independent predictor for ox-LDL concentration (p<0.001). Known mutations were not found in all FH cases except for few insignificant genetic variations which are pThr2515Thr, p.Ile2716Ile, p.Pro2739Leu, p.Glu4181Lys, p.Arg4270Thr, p.Arg4297His and p.Ser4338Asn. These findings demonstrate that FH patients have higher oxidative stress concentration which suggests a greater risk of developing atherosclerosis. These results provide additional knowledge regarding FH in Malaysians.
format	Thesis
qualification_level	Master's degree
author	Hamzan, Nur Suhana
author_facet	Hamzan, Nur Suhana
author_sort	Hamzan, Nur Suhana
title	Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan
title_short	Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan
title_full	Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan
title_fullStr	Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan
title_full_unstemmed	Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan
title_sort	status of oxidative stress and characterization of apob gene mutation in patients with familial hypercholesterolaemia / nur suhana hamzan
granting_institution	Universiti Teknologi MARA (Kampus Sg. Buloh)
granting_department	Faculty of Medicine
publishDate	2016
url	https://ir.uitm.edu.my/id/eprint/62287/1/62287.pdf
_version_	1783735251258834944

Status of oxidative stress and characterization of APOB Gene Mutation in patients with Familial Hypercholesterolaemia / Nur Suhana Hamzan

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