MRC PhD student

Level of study: PhD

Title: Expression behaviour of selected lipid metabolism genes in response to niacin in the African green monkey and the implications for humans

Project summary:
Atherothrombotic vascular disease continues to be a leading cause of morbidity and mortality in much of the world. Although a healthy lifestyle and the lowering of low-density lipoprotein (LDL) cholesterol significantly reduce cardiovascular morbidity and mortality, substantial number of adverse atherothrombotic events continues to occur. These facts highlight the need for additional therapies to manage atherosclerosis and thrombosis. In this regard, high-density lipoprotein (HDL)-based therapies have recently become the focus of attention which is shifting from lowering of the lipid ‘numbers’ to an emphasis on vascular biology, pharmacogenetics and a greater understanding of the importance of HDL cholesterol. This approach relies on the identification of genetic variants, which influence risk factors. In this century most major medical advances have resulted in part from research on animals and non-human primates such as the African green monkey and therefore often serve as a critical link between basic research and human clinical application. The establishment of suitable animal models for the study of human disease has proven to be invaluable for the study of human cardiovascular disease. In this study, the African green monkey is used as a model to examine gene expression and the influence of several polymorphisms found in genes that are involved in cholesterol metabolism in humans.

To further understand the mechanism of cholesterol metabolism and to better define the molecular genetics of the African green monkey, pharmacogenetic techniques were employed in this study to deal with the influence of genetic variation on drug response (niacin) by correlating gene expression or single-nucleotide polymorphisms with a drug’s efficacy or toxicity. Results obtained from this study will be used as a reference to human studies.

Supervisors: Dr Jürgen Seier, Dr Zainunisha Arieff and Dr Mandeep Kaur
Study Institution: University of the Western Cape
MRC Primate Unit