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  • Clinical Implications
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Clinical Implication

Clinical implications of pharmacogenomics of statin treatment

The Pharmacogenomics Journal volume 6, pages 360–374 (2006)Cite this article

β-hydroxy-β-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors, or statins, inhibit endogenous cholesterol production by competitive inhibition of HMG-CoA reductase (HMGCR), the enzyme that catalyzes conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol synthesis. By reducing intracellular cholesterol production, statin treatment results in upregulation of low-density lipoprotein (LDL) receptors, leading to increased plasma clearance of LDL, primarily by the liver. In addition, statins can reduce hepatic secretion of the ApoB-containing lipoproteins, very low-density lipoprotein (VLDL) and LDL. As a result of these effects, statins can reduce plasma levels of atherogenic LDL by as much as 50%. Other effects of potential clinical significance include reductions in plasma triglycerides (TGs), increases in high-density lipoprotein (HDL) cholesterol (HDLC), an indicator of reduced cardiovascular disease (CVD) risk, and reductions in inflammatory markers, notably C-reactive protein (CRP), that have been implicated in the development of CVD.

Statin therapy has been shown in numerous large clinical trials to reduce risk of cardiovascular events by 20–30%, an effect strongly related to the magnitude of LDL cholesterol (LDLC) reduction.1, 2 On the basis of these findings, statin treatment in conjunction with lifestyle changes is indicated as first-line therapy for prevention of CVD in individuals who are considered to be at risk.3 Adoption of current guidelines for plasma LDL reduction has led to the widespread and increasing use of statins, which are now the most prescribed class of drugs worldwide.

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Acknowledgements

This work was supported by Pharmacogenetics Research Network Grants U-01 HL-69757, funded by the National Heart Lung and Blood Institute, and U-01 GM-61374, funded by the National Institute of General Medicine Sciences.

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  1. Department of Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, CA, USA

    L M Mangravite & R M Krauss

  2. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA

    C F Thorn

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  1. L M Mangravite
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Mangravite, L., Thorn, C. & Krauss, R. Clinical implications of pharmacogenomics of statin treatment. Pharmacogenomics J 6, 360–374 (2006). https://doi.org/10.1038/sj.tpj.6500384

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