The genetic determinants of atorvastatin response.
The statins or HMG-CoA reductase inhibitors are considered one of the most effective classes of drugs for reducing LDL and total cholesterol. Although, statin treatment has beneficial effects in the prevention of cardiovascular disease, considerable inter-individual variation exists in response to statin therapy, as well as in the incidence of adverse effects. Genetic factors contribute to patients' inter-variability in the lipid-lowering response to statins,drug-interactions and the occurrence of muscle damage havebeen reported. However, studies investigating aspects of pharmacokinetics, pharmacodynamics and disease-related genes have found no association that could impact on the decisions to treat with statins. Improved strategies that assess the simultaneous influence of multiple relevant susceptibility factors on disease risk (eg, diet, lifestyle and gene effects) are required. Data from pharmacogenetics studies investigating the association between gene variation and drug response and/or susceptibility to adverse effects are promising and are expected to impact on the clinical treatment of hypercholesterolemia.
Rodrigues
Alice C
AC
University of Sao Paulo, Department of Clinical and Toxicological Analysis, Av Prof Lineu Prestes, 580, Sao Paulo, SP 05508-900, Brazil. alice-rodrigues@uol.com.br
Hirata
Mário H
MH
Hirata
Rosario D C
RD
D000818:Animals; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D006538:Heptanoic Acids / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D009135:Muscular Diseases / Q000139:chemically induced / Q000235:genetics*; D011758:Pyrroles / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012307:Risk Factors
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin