Pharmacogenetics of lipid diseases.
The genetic basis for most of the rare lipid monogenic disorders have been elucidated, but the challenge remains in determining the combination of genes that contribute to the genetic variability in lipid levels in the general population; this has been estimated to be in the range of 40-60 per cent of the total variability. Therefore, the effect of common polymorphisms on lipid phenotypes will be greatly modulated by gene-gene and gene-environment interactions. This approach can also be used to characterise the individuality of the response to lipid-lowering therapies, whether using drugs (pharmacogenetics) or dietary interventions (nutrigenetics). In this regard, multiple studies have already described significant interactions between candidate genes for lipid and drug metabolism that modulate therapeutic response-although the outcomes of these studies have been controversial and call for more rigorous experimental design and analytical approaches. Once solid evidence about the predictive value of genetic panels is obtained, risk and therapeutic algorithms can begin to be generated that should provide an accurate measure of genetic predisposition, as well as targeted behavioural modifications or drugs of choice and personalized dosages of these drugs.
Ordovas
Jose M
JM
Nutrition and Genomics Laboratory, Jean Mayer-United States Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. jose.ordovas@tufts.edu
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001161:Arteriosclerosis / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics; D002784:Cholesterol / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008055:Lipids / Q000235:genetics*; D008954:Models, Biological; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D001057:Apolipoproteins E; D000960:Hypolipidemic Agents; D008055:Lipids; D002784:Cholesterol