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Abstract
Pharmacogenetics or pharmacogenomics approaches are important for addressing the individual variabilities of drug efficacy especially in the era of precision medicine. One particular interesting gene to investigate is APOA5, which has been repeatedly linked with the inter-individual variations of serum triglycerides. Here, we explored APOA5-statin interactions in 195 Chinese subjects randomized to rosuvastatin (5–10 mg/day), atorvastatin (10–20 mg/day), or simvastatin (40 mg/day) for 12 weeks by performing a targeted genotyping analysis of the APOA5 promoter SNP rs662799 (-1131T > C). There were no significant differences between the treatment arms for any of the statin-induced changes in clinical biomarkers. Reductions in LDL cholesterol were influenced by the APOA5 genotype in all three treatment groups. By contrast, changes in HDL cholesterol, and triglycerides were only affected by the APOA5 genotype in the atorvastatin and simvastatin groups and not in the rosuvastatin group. Our results suggest that future studies may need to consider stratifying subjects not only by genetic background but also by prescribed statin type.
Highlights
Statins are the most prescribed class of drugs worldwide for prevention of various cardiovascular diseases
To determine how APOA5 variations were associated with the clinical responses of the three statins, we investigated how changes in the biomarker concentrations in response to each statin varied among the three APOA5 genotypes (Figures 1B–E and Supplementary Table S1)
Our pilot study revealed that rosuvastatin achieved comparable improvements in all biomarkers examined despite the fact that it was prescribed at a much lower dose than atorvastatin and simvastatin
Summary
Statins are the most prescribed class of drugs worldwide for prevention of various cardiovascular diseases. About one third of patients do not respond well to this therapy with respect to the lipid-lowering effect, suggesting that pharmacogenomics (Postmus et al, 2014) or other environmental factors such as diet (Jenkins et al, 2005) or the gut microbiome (Kaddurah-Daouk et al, 2011) may play substantial roles. Genome-wide association studies have identified at least 39 genes that are associated with statin treatment efficacy (Gryn and Hegele, 2014). Most of these genes are involved in either the direct pharmacokinetic handling of statins or in lipid metabolism pathways especially those involving cholesterol, the main target of statin therapy (Mangravite et al, 2006). Accumulating evidence indicates that statins can lower. APOA5 and Statin Interactions levels of triglycerides, potentially through altering degradation of apolipoprotein B (ApoB) and related very low-density lipoprotein (VLDL) balance, the precise mechanism remains unclear (Ginsberg et al, 1987; Arad et al, 1992; Ginsberg, 1998)
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