The role of lipids in cardiovascular disease: lessons from rare mutations and special populations.
OBJECTIVE
To review approaches to determining the genetic basis of atherogenesis, the interaction of genes with the environment and with other genes, and the contribution to knowledge of data from subjects with rare mutations and from genetically isolated populations.


METHODS
Current literature, including studies of Canadian families with genetic mutations by the author, on the role of genetic factors in dyslipidemia and atherosclerosis.


METHODS
Studies that have shown effects of gene products on plasma levels of cholesterol and lipids and subsequent atherogenesis.


RESULTS
Studies in families with rare mutations indicate that a single genetic change has a profound effect on phenotype, but the possible clinical application of this information is restricted mainly to members of the extended family. In contrast, studies carried out in large populations show that many genetic factors each have a small impact on phenotype and that these effects are further obscured by environmental factors. The clinical relevance of such findings is unclear.


CONCLUSIONS
Ideally, the information gained from new molecular approaches to identifying the determinants of the intermediate phenotypes of atherosclerosis should be integrated into evidence-based practice. However, the complicating factors are formidable. The use of genetic information to identify subjects at high risk of the clinical end points of atherosclerosis and to enhance health care delivery to such subjects is questionable.
Hegele
R A
RA
Department of Medicine, University of Toronto, Ont. robert.hegele@utoronto.ca
D001161:Arteriosclerosis / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood*; D009154:Mutation
D008074:Lipoproteins