Influence of APOA5 locus on the treatment efficacy of three statins: evidence from a randomized pilot study in Chinese subjects

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 support earlier findings indicating that rosuvastatin is a better treatment option and that future studies should consider stratifying subjects not only by genetic background but also by statin type. Abbreviations ApoA5 apolipoprotein A5 BMI body mass index FFA free fatty acids HDLc high-density lipoprotein cholesterol LDLc low-density lipoprotein cholesterol Lp(a) lipoprotein(a) SNP single nucleotide polymorphism T2D type 2 diabetes Tc total cholesterol Tg triglycerides.