Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur

Glaucoma is a common optic neuropathy. It is the second common cause of blindness. The molecular basis of primary open-angle glaucoma (POAG) is not fully understood. Thus, this study aims to examine the polymorphisms of antioxidant genes and to establish a predictive model based on the metabolite pr...

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Main Author:	Mohamed Bannur, Zakaria
Format:	Thesis
Language:	English
Published:	2014
Online Access:	http://ir.uitm.edu.my/id/eprint/16470/ http://ir.uitm.edu.my/id/eprint/16470/1/TM_ZAKARIA%20MOHAMED%20BANNUR%20MD%2014_5.pdf

id	uitm-16470
recordtype	eprints
spelling	uitm-164702019-02-21T06:52:17Z http://ir.uitm.edu.my/id/eprint/16470/ Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur Mohamed Bannur, Zakaria Glaucoma is a common optic neuropathy. It is the second common cause of blindness. The molecular basis of primary open-angle glaucoma (POAG) is not fully understood. Thus, this study aims to examine the polymorphisms of antioxidant genes and to establish a predictive model based on the metabolite profiles using both genomics and metabolomics approaches. A total of 252 healthy volunteers and 23 POAG patients were recruited. Blood and serum samples were collected. Allele specific-PCR was developed and validated. The technique was efficient to detect genetic variations of antioxidant genes. Manganese superoxide dismutase polymorphism (Val16Ala) showed higher frequency in POAG patients. Val genotype/allele was found to be significantly higher among Chinese. No polymorphisms of catalase (C262T) and glutathione peroxidase (P200L) were detected. Thirty eight different metabolites were detected by global metabolomics. Molecular feature extraction, data filtering, and statistical analysis [/?-value <0.01 (unpaired t-test) and 2-folds change, ANOVA and PCA were able to differentiate metabolites expression between the two groups. Glycine-conjugated bile acids, palmitoylcamitine, inosine, and Pureidoisobutyric acid were increased in POAG patients. These metabolites indicate oxidative stress states. A predictive model using metabolites profiles was developed and validated. It discriminated each group in separate clustering. An overall predictive accuracy of 96.7% was obtained by this model. Ten features model was the best with highest sensitivity and specificity (AUC =0.999, Cl 0.991-1). The model testing resulted in predictive accuracy around 0.95 (AUC= 0.985 95% Cl: 0.944-1), and empirical P< 0.002 at 1000 times permutation test. This pilot study provides further evidence on the involvement of oxidative stress in POAG. The predictive model would be applicable after further validation. This generates new hypothesis for designing medicine and substantial improvements in patients’ clinical outcomes. 2014 Thesis NonPeerReviewed text en http://ir.uitm.edu.my/id/eprint/16470/1/TM_ZAKARIA%20MOHAMED%20BANNUR%20MD%2014_5.pdf Mohamed Bannur, Zakaria (2014) Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur. Masters thesis, Universiti Teknologi MARA.
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Teknologi MARA
building	UiTM Institutional Repository
collection	Online Access
language	English
description	Glaucoma is a common optic neuropathy. It is the second common cause of blindness. The molecular basis of primary open-angle glaucoma (POAG) is not fully understood. Thus, this study aims to examine the polymorphisms of antioxidant genes and to establish a predictive model based on the metabolite profiles using both genomics and metabolomics approaches. A total of 252 healthy volunteers and 23 POAG patients were recruited. Blood and serum samples were collected. Allele specific-PCR was developed and validated. The technique was efficient to detect genetic variations of antioxidant genes. Manganese superoxide dismutase polymorphism (Val16Ala) showed higher frequency in POAG patients. Val genotype/allele was found to be significantly higher among Chinese. No polymorphisms of catalase (C262T) and glutathione peroxidase (P200L) were detected. Thirty eight different metabolites were detected by global metabolomics. Molecular feature extraction, data filtering, and statistical analysis [/?-value <0.01 (unpaired t-test) and 2-folds change, ANOVA and PCA were able to differentiate metabolites expression between the two groups. Glycine-conjugated bile acids, palmitoylcamitine, inosine, and Pureidoisobutyric acid were increased in POAG patients. These metabolites indicate oxidative stress states. A predictive model using metabolites profiles was developed and validated. It discriminated each group in separate clustering. An overall predictive accuracy of 96.7% was obtained by this model. Ten features model was the best with highest sensitivity and specificity (AUC =0.999, Cl 0.991-1). The model testing resulted in predictive accuracy around 0.95 (AUC= 0.985 95% Cl: 0.944-1), and empirical P< 0.002 at 1000 times permutation test. This pilot study provides further evidence on the involvement of oxidative stress in POAG. The predictive model would be applicable after further validation. This generates new hypothesis for designing medicine and substantial improvements in patients’ clinical outcomes.
format	Thesis
author	Mohamed Bannur, Zakaria
spellingShingle	Mohamed Bannur, Zakaria Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur
author_facet	Mohamed Bannur, Zakaria
author_sort	Mohamed Bannur, Zakaria
title	Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur
title_short	Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur
title_full	Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur
title_fullStr	Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur
title_full_unstemmed	Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur
title_sort	oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / zakaria mohamed bannur
publishDate	2014
url	http://ir.uitm.edu.my/id/eprint/16470/ http://ir.uitm.edu.my/id/eprint/16470/1/TM_ZAKARIA%20MOHAMED%20BANNUR%20MD%2014_5.pdf
first_indexed	2023-09-18T22:56:09Z
last_indexed	2023-09-18T22:56:09Z
_version_	1777417866775101440

Oxidative stress in primary open angle glaucoma: relevance of genetic polymorphisms of antioxidant genes and differential metabolite profiles / Zakaria Mohamed Bannur

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