From a public health perspective there is considerable interest in nutrigenetics because it offers potential for reducing penetrance of high risk genotypes/ haplotypes via focused ( individualised ) dietary change. However, the underpinning science is yet in its infancy, with need for studies at a number of levels: (1) epidemiological studies to identify putative genotype-disease associations (e.g. The Wellcome Trust Case-Control Consortium); (2) unequivocal demonstration of the efficacy of diet to reduce/ reverse adverse effects of genotype on risk biomarkers, and; (3) demonstration of the molecular basis of the genotype/ phenotype association. The specific goals of the present research are to: 1) quantify, using a controlled dietary intervention trial, with prospective recruitment according to genotype, the impact of the apoE genotype on the responsiveness of LDLC to dietary fat manipulation, 2) verify the ability of dietary fat manipulation to reduce risk of CHD in carriers o f the apoE4 variant, 3) investigate, using a range of ex vivo techniques, the molecular basis of these genotype-dietary fat-LDLC associations, 4) establish prospective genotypying/ haplotyping as the gold standard for verifying putative (common) genotype-phenotype associations where there is potential for modifying disease risk through lifestyle modification.