title: Pharmacogenetic Foundations of Therapeutic Efficacy and Adverse Events of Statins.
abstract: BACKGROUND
  In the era of precision medicine, more attention is paid to the search for predictive markers of treatment efficacy and tolerability. Statins are one of the classes of drugs that could benefit from this approach because of their wide use and their incidence of adverse events.
  
  
  METHODS
  Literature from PubMed databases and bibliography from retrieved publications have been analyzed according to terms such as statins, pharmacogenetics, epigenetics, toxicity and drug-drug interaction, among others. The search was performed until 1 October 2016 for articles published in English language.
  
  
  RESULTS
  Several technical and methodological approaches have been adopted, including candidate gene and next generation sequencing (NGS) analyses, the latter being more robust and reliable. Among genes identified as possible predictive factors associated with statins toxicity, cytochrome P450 isoforms, transmembrane transporters and mitochondrial enzymes are the best characterized. Finally, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) transporter seems to be the best target for future studies. Moreover, drug-drug interactions need to be considered for the best approach to personalized treatment.
  
  
  CONCLUSIONS
  Pharmacogenetics of statins includes several possible genes and their polymorphisms, but muscular toxicities seem better related toSLCO1B1variant alleles. Their analysis in the general population of patients taking statins could improve treatment adherence and efficacy; however, the cost-efficacy ratio should be carefully evaluated.
authors.affiliation: Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy. elena.arrigoni@hotmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Arrigoni
authors.affiliation: Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy. marzia.delre@ao-pisa.toscana.it.
authors.forename: Marzia
authors.initials: M
authors.lastname: Del Re
authors.affiliation: Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy. leofidilio@gmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fidilio
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy. stefano.fogli@farm.unipi.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fogli
authors.affiliation: Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy. romano.danesi@unipi.it.
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.affiliation: Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy. antonello.dipaolo@med.unipi.it.
authors.forename: Antonello
authors.initials: A
authors.lastname: Di Paolo
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D057890:Epigenomics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D057285:Precision Medicine
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C503999:SLCO1B1 protein, human; D003577:Cytochrome P-450 Enzyme System
keywords: drug transporters; epigenetics; pharmacogenetics; statins; toxicity