Pharmacogenomics and Pharmacogenetics of Cholesterol-Lowering Therapy
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Gerd Schmitz
Abstract
Cholesterol-lowering therapy is the central approach in the primary and secondary prevention of cardiovascular disease, the leading cause of death in industrialized countries. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are currently the most potent and widely used cholesterol-lowering drugs. Large-scale clinical trials unequivocally demonstrated the efficacy of statin treatment in reducing the risk of cardiovascular events. In general, HMG-CoA reductase inhibitors are well tolerated, although in a minority of patients severe adverse effects like myopathy or rhabdomyolysis may develop. The incidence of this potentially life-threatening side effects increases with co-adminstration of drugs that are metabolized via the same pharmacokinetic pathways or at high-dose statin therapy. The recent focus on the pleiotropic effects of statins that are more frequently observed at higher doses and the conclusion drawn from the large statin trials that low-density lipoprotein (LDL)-cholesterol is “the lower the better”, may need careful consideration in individuals at risk of adverse drug reactions. On the other hand, not all patients respond to statin therapy with a reduction in coronary heart disease (CHD) risk. It is therefore of interest to develop diagnostic test systems, which would allow to identify patients at increased risk of adverse drug reactions or patients with a lack of therapeutic effect. Beside exogenous factors, genetic variability determines the response of an individual to drug therapy and the analysis of genetic variants affecting pharmacokinetic or pharmacodynamic aspects of drug therapy is the subject of pharmacogenomics. This review summarizes current knowledge of the pharmacology and the pharmacogenomics of statin therapy.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- First Santorini Conference: From Genetic Variations to Risk Prediction and Pharmacogenomics
- Pharmacogenetics and Pharmacogenomics in Drug Discovery and Development: An Overview
- Regulatory Gene Mutations Affecting Apolipoprotein Gene Expression: Functions and Regulatory Behavior of Known Genes May Guide Future Pharmacogenomic Approaches to Therapy
- The Proteome: Anno Domini 2002
- Cardiac Sodium Channel Diseases
- Haemophilia B: From Molecular Diagnosis to Gene Therapy
- The Use of Denaturing High-Performance Liquid Chromatography (DHPLC) for the Analysis of Genetic Variations: Impact for Diagnostics and Pharmacogenetics
- Molecular Diagnostics by Microelectronic Microchips
- Molecular Beacons as Diagnostic Tools: Technology and Applications
- Electrochemical DNA Sensor for Detection of Single Nucleotide Polymorphisms
- Comparison of Standard PCR and the LightCycler® Technique to Determine the Thrombophilic Mutations: An Efficiency and Cost Study
- Impact of Purified Water Quality on Molecular Biology Experiments
- Which Are the best Tools for Specific Clinical Application (Chips, Multiplex, Mass Spec Profile, etc.)?
- Genetic Variations Observed in Arterial and Venous Thromboembolism – Relevance for Therapy, Risk Prevention and Prognosis
- The TNF- α Gene NcoI Polymorphism at Position –308 of the Promoter Influences Insulin Resistance, and Increases Serum Triglycerides after Postprandial Lipaemia in Familiar Obesity
- The –308 G/A Tumor Necrosis Factor-α Gene Dimorphism: A Risk Factor for Unstable Angina
- The Apolipoprotein AV Gene and Diurnal Triglyceridaemia in Normolipidaemic Subjects
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- Analysis of Multiple Single Nucleotide Polymorphisms of Candidate Genes Related to Coronary Heart Disease Susceptibility by Using Support Vector Machines
- PON1-192 Phenotype and Genotype Assessments in 918 Subjects of the Stanislas Cohort Study
- Lipoprotein Lipase Gene Polymorphisms in Croatian Patients with Coronary Artery Disease
- Homocysteine, Methylenetetrahydrofolate Reductase C677T Polymorphism and the B-Vitamins: A Facet of Nature-Nurture Interplay
- Which, and How Limited Number of Polymorphisms Should Be Selected per Disease, Risk Assessment, Health Profile or Biological System?
- Ethical Issues: Should We Give the Predictive Genetic Profile to the Citizens?
- Pharmacogenetics and Responders to a Therapy: Theoretical Background and Practical Problems
- Pharmacogenetics of Drug Metabolising Enzymes: Importance for Personalised Medicine
- Pharmacogenomics and Pharmacogenetics of Cholesterol-Lowering Therapy
- Pharmacogenomics of Drugs Affecting the Cardiovascular System
- Allele Frequencies for Glutathione S-Transferase and N-Acetyltransferase 2 Differ in African Population Groups and May Be Associated With Oesophageal Cancer or Tuberculosis Incidence
- CYP3A4*1B and NAT2*14 Alleles in a Native African Population
- Pharmacogenetics: From Bench to Bedside
- Meetings and Awards
