Role of Genetic Factors in Statins Side-Effects

Abstract

Statins are relevant drugs involved in the reduction of cardiovascular events both in primary and secondary prevention. Related muscular side-effects are the most common cause of withdrawal and statins discontinuation could induce a negative rebound effect in terms of vascular events. Among factors in association with statins side-effects the combination with other drugs and the female sex are established conditions. However recent data suggest a specific genetic influence in intolerance development, at least for some statins. Indeed a genome-wide study in patients treated with simvastatin found an impressive association between single-nucleotide polymorphisms (SNPs) located within SLCO1B1 gene on chromosome 12 and established myopathy. Furthermore, the association between the SLCO1B1*5 variant and side-effects was found also in patients treated with atorvastatin but not, apparently, with pravastatin and categorized as carriers of mild-myopathy. Recently a similar evidence has been suggested in type 2 diabetic patients treated mainly with simvastatin. However another relevant issue is that, apart from genetic influence in liver transporters influencing drug levels, the complexity of mechanisms involved in the muscular side effects of statins has been addressed by the evidence of other influencing pathways such as the variant within the COQ2 gene involved in Coenzyme Q(10) mild-asymptomatic deficiency and skeletal muscle drug transporters expression. In conclusion, the picture of putative pharmacogenetic modulation of statins safety is reaching a growing body of evidence for translation into clinical practice but more specific studies for each single statin, in different clinical settings, both from genome-wide or competitive candidate genes evaluation, are needed before describing a definitive class-risk profile.

ABCG2 Gene Polymorphisms as Risk Factors for Atorvastatin Adverse Reactions: A Case–Control Study

“…All patients were of Croatian ancestry. Median (interquartile range) age was 56 (48-66) and 60 (53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70) in the groups of patients with and without ADRs, respectively. The gender distribution was identical, and atorvastatin median prescribed dose was the same in both groups.…”

“…For patients at an increased risk of cardiovascular disease (CVD) who have been prescribed statins, it is crucial to be compliant with their therapy. Statin-related muscular side effects are the most common cause of withdrawal and statin discontinuation could induce increased vascular events [57]. Currently there is no direct clinical evidence that the personalized prescribing of statins using genotyping will improve patients' medication adherence; however, previous analyses suggest that this is a logical conclusion [58].…”

State of Play of Pharmacogenetics and Personalized Medicine in Heart Failure

“…Genome‐wide association study has identified SNPs relevant to the management of other cardiovascular diseases . Candidate gene studies are intrinsically limited.…”

The Future of Pharmacogenetics in the Treatment of Heart Failure

“…Genome wide association studies (GWAS) provide a mechanism for discovering relevant genetic loci and have identified drug-gene interactions in treatment of other cardiovascular diseases (61)(62). To date virtually no published GWAS has sought relevant genes in HF drug response, GWAS have been used to identify loci implicated in the development of HF and outcome in patients with HF (63-65).…”