Pharmacogenomics of response to statin treatment and susceptibility to statin-induced adverse drug reactions in Asians: a scoping review

Abstract

Background: Statins are the most widely used lipid-lowering agents for patients with hyperlipidemia. However, interindividual variations in efficacy and risk of adverse drug reactions to statin treatment have been widely reported. Ethnicity is well known to be one of the contributing factors to this variation, particularly among Asians.

Objectives: To identify genetic variants associated with statin treatment responses among Asian populations with a focus on four commonly prescribed statins: atorvastatin, rosuvastatin, simvastatin, and pravastatin.

Methods: A literature search was conducted in Medline and Embase databases. Studies published from 2008 to 2021 were included. The title and abstract of each article were screened by two reviewers and verified by another two reviewers. Data charted include information on authors, year of study, study population, statin studied, gene studied, study findings, and data of significant statistical value.

Results: A total of 35 articles were included from the 1,939 original studies related to treatment efficacy and 5 articles out of the 284 original studies related to adverse effects. Genetic variants in transmembrane transporters, cytochrome P450 isoenzymes, and apolipoproteins are the most extensively studied among Asian populations, with a main focus on ethnic Chinese. However, Asia consists of genetically different populations, and the results of this review indicated that there is a paucity of studies on other ethnic groups within Asia.

Conclusions: Considering the ethnicity of patients could provide a potential value to personalized medicine in statin therapy.

Keywords: HMG-CoA reductase inhibitors; HMG-CoA statins; cholesterol; myotoxicity; pharmacogenomics.

Figure 1.

Flow diagram of selection process for scoping review of pharmacogenomics of statin treatment outcomes in Asians based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Figure 2.

Gene polymorphisms significantly affecting the therapeutic response of statins (atorvastatin, rosuvastatin, simvastatin, and pravastatin) in Asian populations. Statins are transported into hepatocytes via active transport through SLC transporters and metabolized mainly by CYP enzymes and eliminated by efflux pumps, ABC proteins. In terms of mechanism of action, statins inhibit HMGCR, which is the step-limiting step in cholesterol synthesis. Created with BioRender.com. Adapted from PharmGKB [8]. ABC, ATP-binding cassette; APO, apolipoprotein; APOA5, Apolipoprotein A-V; APOE, apolipoprotein E; CETP, cholesterol ester transfer protein; CYP, cytochrome P450; CYP7A1, cholesterol 7-α-hydroxylase; HDL, high-density lipoprotein; HMGCR, HMG-CoA reductase; IDL, intermediate-density lipoprotein; LCAT, lecithin-cholesterol acyltransferase; LDL, low-density lipoprotein; LDLR, LDL receptor; LPL, lipoprotein lipase; SLC, solute carrier; VLDL, very-low-density lipoprotein.