Diet, genes and cardiovascular health research
The composition of the diet and the interactive influence of an individual's genetic make-up are recognised as being centrally involved in both the initiation and progression of cardiovascular disease (CVD), the metabolic syndrome and diabetes. In an era of more personalised approaches to cardiovascular disease (CVD) prevention and treatment, nutrigenetics and pharmacogenetics - the branches of genetic research that investigate the influence of genotype on the response to dietary manipulation or prescribed medications - have emerged as major areas of focus in cardiovascular research. Within the ICMR a large volume of research is ongoing which is investigating the impact of a number of foods and nutrients including: saturated, monounsaturated, n-6 polyunsaturated and long chain n-3 polyunsaturated fatty acids (fish oil fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), fruits and vegetables and specific phytochemicals (flavonoids and carotenoids) on many aspects of the cardiovascular phenotype, including lipoprotein metabolism, insulin sensitivity, inflammation and vascular function and reactivity. We are a partner centre of the recently completed RISCK (n=650) and Pan-European LIPGENE studies (n=480), which are the largest human intervention studies conducted to date to investigate the impact of dietary fat and carbohydrate composition and genotype on insulin sensitivity and other metabolic CVD risk factors. The ICMR is a leading nutrigenetics research centre, where we investigate the physiological and molecular mechanisms responsible for the influence of common gene variants (single nucleotide polymorphisms, SNP) or SNP combinations (haplotypes), on the cardiovascular phenotype and the impact of genotype on responsiveness to dietary change. Much of the work conducted to date has focussed on the apolipoprotein E (apoE) genotype. Key findings that have emerged include the identification that a pro-inflammatory and pro-oxidative state is, in large part, likely to explain the increased CVD risk in apoE4 carriers (25% UK population) and that this subgroup is particularly sensitive to the LDL-cholesterol raising effects of saturated fat and high dose fish oil intakes. Other genotypes of interest include gene variants that mediate the postprandial lipaemic response and the eNOS gene, which is responsible for nitric oxide production within the vascular endothelium.
A unique aspect of our scientific approach is the use of human trials to examine physiological effects of dietary change, in combination with a range of cell culture approaches to investigate molecular mechanisms. We have a 10 room clinical facility, which accommodates approximately 1000 volunteers per year, taking part in a range of nutrition trials. The unit houses an extensive range of techniques for the assessment of vascular function, including flow mediated dilation (FMD), laser doppler iontophoresis (LDI), pulse wave analysis (PWA) and pulse wave velocity (PWV). We take a food chain approach to improved population dietary composition and work closely with our Animal Nutrition and Plant Science colleagues to develop food products with enhanced composition.
The vascular reactivity of the brachial vessels in the arm (measured by Laser Doppler Imaging (LDI) with ionotophoresis) of a subject after ingestion of a flavonoid-rich and a control drink is visualized in the 'flux' boxes. The more intense colour indicates a greater vasodilatation. ACh - acetylcholine (stimulates endothelial dependent nitric oxide (NO) production and subsequent endothelium dependent vasodilatation), SNP - sodium nitroprusside (NO donor which stimulates endothelium independent vasodilatation)
