The R563Q mutation of the beta subunit of the epithelial sodium channel : prevalence and effect

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dc.contributor.advisorRayner, B Len_ZA
dc.contributor.advisorOwen, E Pen_ZA
dc.contributor.advisorMeissner, P Nen_ZA
dc.contributor.authorJones, Erika Sherad Wilshireen_ZA
dc.date.accessioned2014-07-29T09:03:59Z
dc.date.available2014-07-29T09:03:59Z
dc.date.issued2009en_ZA
dc.descriptionIncludes abstract.
dc.descriptionIncludes bibliographical references (p. 201-229).
dc.description.abstractHypertension is a major worldwide predictor of morbidity and mortality. The search for genes that contribute to blood pressure is ongoing. The epithelial sodium channel genes were implicated when the beta subunit (SCNN1B, gene ID 6338) was found to have a mutation that caused Liddle’s syndrome. The R563Q mutation in the beta subunit has been associated with hypertension and pre-eclampsia in the Xhosa and Coloured people in Cape Town. The thesis consists of a cross-sectional analysis of the prevalence of the R563Q mutation in multiple ethnic groups in South Africa and a longitudinal functional assessment in response to saline infusion. The objectives were to determine the prevalence of the R563Q mutation and association with hypertension, and if it persists within families; to speculate as to the origins of the mutation; to determine if there were any relevant clinical differences between comparable patients with essential hypertension; to determine if the mutation predicted a difference in response to acute sodium loading and if a physiological difference is observed in sodium channel activity when expressed in oocytes. A high frequency of hypertensives in Johannesburg and Cape Town were found to be heterozygous and the mutation associated with hypertension, including within families. In the Khoisan the R563Q mutation was found at a high frequency (19%) in a random sample, suggesting the mutation originated from this population. The saline challenge illustrated the in vivo effects of the mutation. The results suggest that the sodium channel is innately overactive in heterozygous subjects and that counter-regulatory mechanisms are in place to compensate for changes in renal sodium handling. However, preliminary in vitro testing in oocytes did not show a difference in sodium channel activity.en_ZA
dc.identifier.apacitationJones, E. S. W. (2009). <i>The R563Q mutation of the beta subunit of the epithelial sodium channel : prevalence and effect</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/3404en_ZA
dc.identifier.chicagocitationJones, Erika Sherad Wilshire. <i>"The R563Q mutation of the beta subunit of the epithelial sodium channel : prevalence and effect."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2009. http://hdl.handle.net/11427/3404en_ZA
dc.identifier.citationJones, E. 2009. The R563Q mutation of the beta subunit of the epithelial sodium channel : prevalence and effect. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Jones, Erika Sherad Wilshire AB - Hypertension is a major worldwide predictor of morbidity and mortality. The search for genes that contribute to blood pressure is ongoing. The epithelial sodium channel genes were implicated when the beta subunit (SCNN1B, gene ID 6338) was found to have a mutation that caused Liddle’s syndrome. The R563Q mutation in the beta subunit has been associated with hypertension and pre-eclampsia in the Xhosa and Coloured people in Cape Town. The thesis consists of a cross-sectional analysis of the prevalence of the R563Q mutation in multiple ethnic groups in South Africa and a longitudinal functional assessment in response to saline infusion. The objectives were to determine the prevalence of the R563Q mutation and association with hypertension, and if it persists within families; to speculate as to the origins of the mutation; to determine if there were any relevant clinical differences between comparable patients with essential hypertension; to determine if the mutation predicted a difference in response to acute sodium loading and if a physiological difference is observed in sodium channel activity when expressed in oocytes. A high frequency of hypertensives in Johannesburg and Cape Town were found to be heterozygous and the mutation associated with hypertension, including within families. In the Khoisan the R563Q mutation was found at a high frequency (19%) in a random sample, suggesting the mutation originated from this population. The saline challenge illustrated the in vivo effects of the mutation. The results suggest that the sodium channel is innately overactive in heterozygous subjects and that counter-regulatory mechanisms are in place to compensate for changes in renal sodium handling. However, preliminary in vitro testing in oocytes did not show a difference in sodium channel activity. DA - 2009 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - The R563Q mutation of the beta subunit of the epithelial sodium channel : prevalence and effect TI - The R563Q mutation of the beta subunit of the epithelial sodium channel : prevalence and effect UR - http://hdl.handle.net/11427/3404 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/3404
dc.identifier.vancouvercitationJones ESW. The R563Q mutation of the beta subunit of the epithelial sodium channel : prevalence and effect. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2009 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3404en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherMedicineen_ZA
dc.titleThe R563Q mutation of the beta subunit of the epithelial sodium channel : prevalence and effecten_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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