Genomic Variations Affecting Biological Effects of Statins

Abstract

Background: Statins are inhibitors of hydroxy-methyl-glutaryl coenzymeA (HMG-CoA) reductase, the rate-limiting enzyme involved in de novo cholesterol synthesis. The patient health profile needs to be taken in account during the interpretation of the variability in the outcome of drug therapy, as well as compliance with prescribed pharmacological treatments, and genetic profile.

Objective: Several genetic polymorphisms playing a role in the different response to lipid lowering therapy have recently been identified. Statins, today are used to reduce Low Density Lipoprotein-Cholesterol (LDL-C), represent the treatment of choice in individuals with increased risk of Cardio-Vascular Disease (CVD), both in primary and secondary prevention of cardiovascular events. Regardless of the usefulness in a wide range of patients, the common interindividual genetic variability, along with phenotypic aspects, lead to resistance and adverse responses.

Methods: we reviewed on PubMed, inserting as term search "statin and polymorphism", "statin and pharmacogenomic", "statin and gene", "HMG-CoA reductase and gene".

Results: A large number of candidate genes and many single nucleotide polymorphisms (SNPs) have been evaluated and related to pharmacokinetic and/or pharmacodynamic of statins.

Conclusion: Despite these several findings there is still not enough evidence to recommend pharmacogenomic tests before starting statin therapy.