dc.contributor.advisor | Griffiths, Lyn | |
dc.contributor.author | Fowdar, Javed Youssouf | |
dc.date.accessioned | 2018-01-23T02:23:57Z | |
dc.date.available | 2018-01-23T02:23:57Z | |
dc.date.issued | 2012 | |
dc.identifier.doi | 10.25904/1912/2324 | |
dc.identifier.uri | http://hdl.handle.net/10072/365911 | |
dc.description.abstract | Hypertension, which is defined as persistent high blood pressure, is a major risk factor for cardiovascular diseases and affects more than 1 billion people worldwide. Approximately twenty percent of Australian adults receive treatment for hypertension and thus hypertension is also a major cost to healthcare systems, both in Australia and worldwide. Despite the high burden of hypertension on society, the majority of the risk factors for developing hypertension are still unknown. Though the involvement of environmental factors in hypertension development has been relatively well-characterised, hypertension is a complex polygenic disease of which only a few susceptibility genes have been identified. The broad aims of this research were therefore to identify hypertension susceptibility genes through both a traditional hypothesis-driven approach (candidate gene studies) and through gene discovery methods that do not rely on a priori biological assumptions (genome-wide association studies and pathway analysis studies). Using a combined approach, this research investigated both canonical blood pressure regulation pathways and novel mechanisms for association with hypertension susceptibility. The study utilised a case-control association approach involving Australian hypertensive cases and age-, sex-, and ethnicity-matched controls to investigate specific candidate genes and a more comprehensive genome-wide association study (GWAS) and pathway analysis for novel gene discovery. The candidate gene approach was based on the hypothesis that hyperhomocysteinemia-causing gene variants in enzymes of the homocysteine (Hcy) metabolism pathway increase the risk of hypertension and examined four such markers in three Hcy pathway genes, MTHFR, MTRR, and MTHFD1. Despite some mixed reports on the positive association of hypertension and MTHFR, this approach found no significant association of any of the Hcy gene markers with hypertension either individually or in an epistatic interaction model. | |
dc.language | English | |
dc.publisher | Griffith University | |
dc.publisher.place | Brisbane | |
dc.rights.copyright | The author owns the copyright in this thesis, unless stated otherwise. | |
dc.subject.keywords | Hypertension genes | |
dc.subject.keywords | Hyperhomocysteinemia-causing gene variants | |
dc.subject.keywords | Methylenetetrahydrofolate reductase (MTHFR) | |
dc.subject.keywords | Methionine synthase reductase (MTRR) | |
dc.subject.keywords | Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) | |
dc.title | Identification of Hypertension Genes Following a Genome-Wide Association Scan | |
dc.type | Griffith thesis | |
gro.faculty | Griffith Health | |
gro.rights.copyright | The author owns the copyright in this thesis, unless stated otherwise. | |
gro.hasfulltext | Full Text | |
dc.contributor.otheradvisor | Rose'meyer, Roselyn | |
dc.contributor.otheradvisor | MacGregor, Stuart | |
dc.rights.accessRights | Public | |
gro.identifier.gurtID | gu1374124847854 | |
gro.source.ADTshelfno | ADT0 | |
gro.source.GURTshelfno | GURT1451 | |
gro.thesis.degreelevel | Thesis (PhD Doctorate) | |
gro.thesis.degreeprogram | Doctor of Philosophy (PhD) | |
gro.department | School of Medical Science | |
gro.griffith.author | Fowdar, Javed Y. | |