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Lipid-Lowering Responses Modified by Genetic Variation

  • Chapter
Cardiovascular Pharmacogenetics

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 160))

Abstract

Elevated cholesterol and other dyslipidaemias are major risk factors for atherosclerotic cardiovascular disease—the major cause of death in North America and Europe. Correction of dyslipidaemia with diet or lipid-lowering agents has been shown to reduce the risk of future coronary events. However, the response to diet or lipid-lowering drugs is not uniform within any population. Even among carefully selected patients in clinical trials, individual responses to a lipid-modifying intervention vary greatly. On the one hand, factors such as gender, age, concomitant disease and concomitant medication may modify the pharmacokinetics or pharmacodynamics of lipid-lowering therapy. On the other hand, genetic factors are also important. Polymorphisms in genes regulating the metabolism of lipoproteins (e.g. apolipoprotein E, lipoprotein lipase, cholesteryl ester transfer protein) are associated with differences in plasma lipoprotein concentrations and can explain a substantial fraction of their variance in the general population, as demonstrated in measurements of low-density lipoprotein (LDL) or high-density lipoprotein (HDL). With the widespread availability of molecular genetic testing, the focus has shifted to the study of genetic determinants of drug response and their role in optimizing the choice of agent with regard to efficacy and tolerability. At present, despite several positive, but in general isolated examples, the overall impact of such gene variants in predicting individual response to a lipid-lowering intervention still needs clarification in well-designed confirmatory studies. Advances in pharmacogenomics will help to deepen our understanding of lipid and lipoprotein metabolism and the consideration that needs to be give to genetic factors in prescribing lipid-lowering therapy.

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  1. Kooperationseinheit Pharmakogenomik/Angewandte Genomforschung, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 221, 69120, Heidelberg, Germany

    B. R. Winkelmann

  2. Zentrale Klinische Forschung, Universitätsklinikum, Breisacher Str. 66, 79106, Freiburg, Germany

    M. M. Hoffmann

  3. Clinical Institute of Medical and Chemical Laboratory Diagnostics, University Hospital, Auenbrugger Platz 15, 8036, Graz, Austria

    W. März

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  1. Experimental Medicine & Toxicology Imperial College London, Hammersmith Campus, Du Cane Road, W12 0NN, London, UK

    Martin R. Wilkins (Professor) (Professor)

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Winkelmann, B.R., Hoffmann, M.M., März, W. (2004). Lipid-Lowering Responses Modified by Genetic Variation. In: Wilkins, M.R. (eds) Cardiovascular Pharmacogenetics. Handbook of Experimental Pharmacology, vol 160. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-06214-2_5

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