title: Pharmacogenomics and adverse drug reactions: the case of statins.
abstract: BACKGROUND
  The use of genomics to predict adverse drug reactions (ADRs) has been the subject of much research over the last decade. Concerns about the muscular safety of statins, a highly prescribed group of drugs, are partially related to their high exposure. Many studies have identified a variety of genetic markers related to statin-induced myopathy. However, only polymorphisms in the SLCO1B1 gene (which encodes the carrier responsible for the hepatic uptake of statins, which, in turn, contributes to the regulation of plasma levels of SLCO1B1) were strongly associated with statin-induced muscular adverse effects. These was found to be most prominent for simvastatin. The strength of these findings relies on the use of modern genetic approaches, such as well-designed, case-controlled and genome-wide association studies. Nevertheless, the clinical use of this information is far from known at present and needs to be evaluated.
  
  
  METHODS
  The links between genetic polymorphisms (i.e., SLCO1B1 gene) and statin-induced muscle ADRs and the methodological issues involved in the establishment of such an association are explored.
  
  
  CONCLUSIONS
  Despite there being a statin-gene association for myopathy, in the case of some statins the usefulness of this information still needs to be proven.
authors.affiliation: Department of Cardiology and Cardiovascular Surgery, Montañeses 2325 (1428), FLENI, Buenos Aires, Argentina. marianogiorgi@hotmail.com
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Giorgi
authors.forename: Christian
authors.initials: C
authors.lastname: Caroli
authors.forename: Hernán Cohen
authors.initials: HC
authors.lastname: Arazi
authors.forename: Guillermo
authors.initials: G
authors.lastname: Di Girolamo
mesh_terms: D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D027381:Liver-Specific Organic Anion Transporter 1; D009135:Muscular Diseases / Q000139:chemically induced* / Q000235:genetics; D027361:Organic Anion Transporters / Q000097:blood / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D019821:Simvastatin / Q000009:adverse effects
chemical_list: D005819:Genetic Markers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D019821:Simvastatin