Development and application of a pathology supported genetic assay to assess the impact of hereditary factors on health outcomes in individuals subjected to a wellness screen
Kotze, M J
University of Stellenbosch. Faculty of Health Sciences. Department of Pathology
Kotze, M J
Van Rensburg, S J
Blackhurst, D M
Janse Van Vuuren, A
Socio-economic development has led to a significant increase in chronic non-communicable diseases such as cardiovascular disease (CVD), diabetes and certain forms of cancer. Research performed over recent years has clearly shown that the best ways to avoid cancer are similar to those needed to prevent obesity, insulin resistance and heart disease as well. The association between these conditions and the metabolic syndrome can be explained, at least in part, by genetic alterations in genes involved in the metabolism of endogenous hormones – including insulin and insulin-like growth factors – which can lead to distortion of the normal balance between cell proliferation, differentiation, and apoptosis. Modifiable environmental factors such as diet, exercise and smoking interact with genetic risk factors, causing cumulative effects which may result in disease development.
Diet is considered to be the key environmental factor affecting the incidence of most chronic diseases treated by medical practitioners on a daily basis. Genes determine how individuals respond to food and physical activity. Exhausted antioxidant defences in the human body contribute to oxidative stress and when accumulated (as with ageing) may contribute to disease development. The protection that fruits and vegetables in the diet provide against these diseases may be attributed to their antioxidant activity. Similar effects observed with regular intake of tea and red wine is also ascribed to the anti-oxidants in these beverages. However, individuals with different genetic backgrounds react differently to dietary and lifestyle intervention and alcohol intake may be contra-indicated in some. For example, excessive alcohol intake increase the risk of cancer and is even higher in the presence of mutations in the methyltetrahydrofolate reductase (MTHFR) gene when folate status is low; alcohol intake in the presence of the apolipoprotein E (ApoE) E4 gene variant increases the risk of Alzheimer’s disease; and alcohol increase the absorption of iron that is of specific concern in HFE gene mutation carriers with non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome. Long-term intervention strategies for health promotion including lifestyle modification may therefore be more effective when guided from the genetic background.
The ultimate aim of the current project is to target gene-environment interactions that may cause cumulative effects resulting in increased risk of cancer and heart disease in patients with features of the metabolic syndrome. Health outcomes of patients on a Mediterranean-type diet with or without moderate alcohol intake will be compared between genetic subgroups, prior to the implementation of an individualised lifestyle modification plan guided from the genetic profile of the patient. This will allow us to determine the benefits of participation in a Genomic Health and Wellness Program, which forms an important output of this project.
The objectives are: Development of a cost-effective multi-gene nutrigenetics test to be used as part of a wellness program Development of a gene-based wellness program to reduce the risk of cancer and heart disease in patients with (symptoms of) the metabolic syndrome Development of an Applied Genetics Training Program for clinicians to be registered as a Short Course at the University of Stellenbosch.
Kotze, M J, Van Velden, D P, Kidd, M and Marnewick, J. 2011. Genotype associations in South African patients with metabolic syndrome. Paper presented at the Joint International Conference of the African Society for Human Genetics. 6-9 March, University of Cape Town, Cape Town, South Africa.
De Kock, L, Davis, W, Pretorius, K, Geiger, D, Yako, Y and Kotze, M J. 2011. Development of a single nucleotide polymorphism (SNP) knowledge database: CYP1A2 (rs762551) as a BRCA1 modifier. Paper presented at the Joint International Conference of the African Society for Human Genetics. 6-9 March, University of Cape Town, South Africa.
Kotze, M J, Marnewick, J L, Kidd, M and Van Velden, D P. 2013. Pathology-supported genetic testing directed at shared disease pathways for optimized health in later life. WineHealth 2013: 8th International Congress on Wine and Health Conference. 18-20 July, Sydney, Australia.