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The role of renin-angiotensin-aldosterone system (RAAS) genes in the development of hypertrophy in hypertrophic cardiomyopathy (HCM)
Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : University of Stellenbosch
2009
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| _version_ | 1867613791187894272 |
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| access_status_str | Open Access |
| author | Carstens, N. |
| author2 | Moolman-Smook, J. C. |
| author_browse | Carstens, N. Moolman-Smook, J. C. |
| author_facet | Moolman-Smook, J. C. Carstens, N. |
| author_sort | Carstens, N. |
| collection | Thesis |
| dc_rights_str_mv | University of Stellenbosch |
| description | Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/2667 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:41:45.229Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2009 |
| publishDateRange | 2009 |
| publishDateSort | 2009 |
| publisher | Stellenbosch : University of Stellenbosch |
| publisherStr | Stellenbosch : University of Stellenbosch |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/2667 The role of renin-angiotensin-aldosterone system (RAAS) genes in the development of hypertrophy in hypertrophic cardiomyopathy (HCM) Carstens, N. Moolman-Smook, J. C. Van der Merwe, L. University of Stellenbosch. Faculty of Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics. Modifiers Renin-angiotensin-aldosterone system Hypertrophic cardiomyopathy Heart hyperthrophy therapy Dissertations -- Medicine Theses -- Medicine Biomedical Sciences Molecular Biology and Human Genetics Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009. Hypertrophic cardiomyopathy (HCM), an inherited primary cardiac disorder mostly caused by defective sarcomeric proteins, is considered a model for studying left ventricular hypertrophy (LVH) in the absence of increased external loading conditions. The disease manifests extreme variability in the degree and pattern of LVH, even in HCM patients with the same causal mutation. The clinical phenotype of HCM can therefore be viewed as a product of the effect of sarcomere dysfunction and of additional genetic modifiers. Components of the renin-angiotensin-aldosterone system (RAAS) are plausible candidate modifiers because of their effect on blood pressure and their direct hypertrophic effect on cardiomyocytes. The present study investigated genes encoding components of the RAAS for association with cardiac hypertrophy traits, in 353 individuals comprised of genetically and echocardiographically affected and unaffected family members, belonging to 22 HCM families with HCM founder mutations by employing a multi-SNP approach with TaqMan allelic discrimination technology. Gene-gene interaction analysis was also performed to investigate the effect of epistasis on hypertrophy. Candidate genes for analysis included the angiotensin II type 2 receptor (AT2 receptor), renin, renin-binding protein (RnBP), the (pro)renin receptor, the mineralocorticoid receptor as well as genes encoding subunits of the epithelial sodium channels (ENaC) and Na+/K+-ATPase that showed evidence for cardiac expression. The present study demonstrates for the first time that variations in the renin and RnBP genes play a role in modulating hypertrophy in HCM, independent of blood pressure and confirms the involvement of the AT2 receptor in hypertrophy in HCM. Additionally we report an association between Na+/K+-ATPase α1- and β1-subunits as well as the ENaC α- and β-subunits and hypertrophy. Significant evidence for epistasis was found between renin and downstream RAAS effectors, suggesting a complex interplay between these RAAS variants and the hypertrophic phenotype in HCM. The identification of such modifiers for HCM may offer novel targets for hypertrophy research and ultimately antihypertrophic therapy. 2009-02-24T09:44:56Z 2010-06-01T08:54:49Z 2009-02-24T09:44:56Z 2010-06-01T08:54:49Z 2009-03 Thesis http://hdl.handle.net/10019.1/2667 en University of Stellenbosch application/pdf Stellenbosch : University of Stellenbosch |
| spellingShingle | Modifiers Renin-angiotensin-aldosterone system Hypertrophic cardiomyopathy Heart hyperthrophy therapy Dissertations -- Medicine Theses -- Medicine Biomedical Sciences Molecular Biology and Human Genetics Carstens, N. The role of renin-angiotensin-aldosterone system (RAAS) genes in the development of hypertrophy in hypertrophic cardiomyopathy (HCM) |
| title | The role of renin-angiotensin-aldosterone system (RAAS) genes in the development of hypertrophy in hypertrophic cardiomyopathy (HCM) |
| title_full | The role of renin-angiotensin-aldosterone system (RAAS) genes in the development of hypertrophy in hypertrophic cardiomyopathy (HCM) |
| title_fullStr | The role of renin-angiotensin-aldosterone system (RAAS) genes in the development of hypertrophy in hypertrophic cardiomyopathy (HCM) |
| title_full_unstemmed | The role of renin-angiotensin-aldosterone system (RAAS) genes in the development of hypertrophy in hypertrophic cardiomyopathy (HCM) |
| title_short | The role of renin-angiotensin-aldosterone system (RAAS) genes in the development of hypertrophy in hypertrophic cardiomyopathy (HCM) |
| title_sort | role of renin angiotensin aldosterone system raas genes in the development of hypertrophy in hypertrophic cardiomyopathy hcm |
| topic | Modifiers Renin-angiotensin-aldosterone system Hypertrophic cardiomyopathy Heart hyperthrophy therapy Dissertations -- Medicine Theses -- Medicine Biomedical Sciences Molecular Biology and Human Genetics |
| url | http://hdl.handle.net/10019.1/2667 |
| work_keys_str_mv | AT carstensn theroleofreninangiotensinaldosteronesystemraasgenesinthedevelopmentofhypertrophyinhypertrophiccardiomyopathyhcm AT carstensn roleofreninangiotensinaldosteronesystemraasgenesinthedevelopmentofhypertrophyinhypertrophiccardiomyopathyhcm |