Low-density lipoprotein heterogeneity.
As a key feature of the ALP, a raised level of small, dense LDL forms part of what is potentially the most common collection of lipoprotein abnormalities to influence the risk of CHD in the general population. The consistency of the association between a prevalence of small, dense LDL and increased risk of CHD is impressive, though the practical constraints of our current methods would limit the clinical application of this information for screening purposes. This highlights the need to elucidate the underlying metabolic and genetic determinants of LDL heterogeneity and to develop alternative forms of analysis based on the structural and functional properties of LDL subclasses and their genotypes. The relationship between enhanced post-prandial lipaemia and raised VLDL is of particular relevance in providing insight into the way in which diet and drugs may target LDL heterogeneity via the insulin-dependent regulation of the post-prandial response. In alluding to the impact of genetic influences on LDL subclasses, twin studies identify a major role for environmental factors as determinants of LDL heterogeneity and, more importantly, as modulators of environmentally susceptible genes. The potential for interactions between dietary factors alone and putative LDL heterogeneity genes is considerable and yet poorly understood, as, for example, the reduced penetrance of the 'ATHS' gene caused through variation in dietary fat and carbohydrate (Nishina et al, 1992). Finally, small, dense LDL has been implicated in at least two major steps of the atherogenic process. Elucidation of the molecular basis of these interactions will be crucial for the identification of genetically susceptible individuals and in the design of appropriate diets and treatment to reduce the risk of CHD mediated through LDL.
Griffin
B A
BA
School of Biological Sciences, University of Surrey, Guildford, UK.
D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology; D003327:Coronary Disease / Q000097:blood / Q000209:etiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000145:classification* / Q000235:genetics; D010641:Phenotype; D012307:Risk Factors
D008077:Lipoproteins, LDL