- Added 29 Apr 2013
Hypertension in Africa: Improving health by genetic profiling and targeted therapy
This study aims to identify inherited mechanisms that cause hypertension in Black Africans by the application of Next Generation Sequencing (NGS) technology and to develop an individualised tailored treatment using the most effective drug class for each patient. It is also possible that novel mechanisms will be revealed which would require bespoke therapies for this population. In addition, we propose to study blood pressure variability among Black Africans resident in Africa because epidemiological evidence suggests that BP variability and instability are important risks factors for vascular events. This study will provide further insights into the greater susceptibility to hypertension and related complications in populations of African ancestry. Knowledge of the genetic mechanisms will guide the appropriate treatment choice leading to better control of hypertension in Blacks and a concomitant improvement in health. A successful outcome will have much public health relevance in reducing the burden associated with hypertension (particularly haemorrhagic stroke) in Africa.
Black African patients with hypertension
This is a multi-phase investigation over X years: (depending on time required to recruit sufficient patient numbers). Phase I (proof-of-concept phase) We will investigate the aetiology of the hypertension to improve our knowledge of the pathophysiological mechanism of hypertension in Blacks and the reasons for the poor response to antihypertensives. We will ascertain and collect data (observations (e.g. height; weight), measurements (e.g. 24 hr BP monitoring; ECG) and demographics) and venous blood samples from 1,000 cases and 1,000 controls, recruited from an initial treatment centre. We will measure a series of biochemical (e.g. renin/aldosterone) and physiological traits relevant to HTN and HTN-related complications. We will then extract DNA and perform a genetic variation analysis using Next Generation Sequencing (NGS) methods to search for ancestry-specific susceptibility genes. The results from this pilot phase will form the basis for expanding the study sample size to other African countries as well as expanding the scope of the genetic analysis (phase II). Phase II The study will be extended to other African countries and centres to increase the sample size to 10,000 cases and controls. The genetic analysis will be expanded in terms of sample size and scope (NGS analysis of the whole exome). Phase III Based on new information on genetic variation and HTN in Africans, we will develop an aetiology-specific therapeutic approach to identify the most effective drug for adequate control of hypertension in Blacks. Outcome measures will include adequately controlled BP, improvement or reduction in hypertension related problems.
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