Pharmacogenetic Foundations of Therapeutic Efficacy and Adverse Events of Statins

• Published in: International journal of molecular sciences Vol. 18; no. 1; p. 104
• Main Authors: Arrigoni, Elena, Del Re, Marzia, Fidilio, Leonardo, Fogli, Stefano, Danesi, Romano, Di Paolo, Antonello
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06-01-2017; MDPI
• Subjects: Animals; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; drug transporters; epigenetics; Epigenomics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - metabolism; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Pharmacogenetics; Polymorphism, Genetic; Precision Medicine; Review; Solute Carrier Organic Anion Transporter Family Member 1b1 - genetics; Solute Carrier Organic Anion Transporter Family Member 1b1 - metabolism; Statins; toxicity; drug transporters; toxicity; statins; epigenetics; pharmacogenetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18010104

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.
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.
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 (
) 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.
Pharmacogenetics of statins includes several possible genes and their polymorphisms, but muscular toxicities seem better related to
variant 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.