Genetic polymorphism and efficacy of high-dose statin therapy

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To evaluate an association between high-dose statins lipid-lowering effect and several single-nucleotide polymorphisms (SNP) of lipid-regulating genes in patients with acute coronary syndrome (ACS).

Material and methods

We recruited 60 patients with ACS with or without ST elevation, who were treated with high dose atorvastatin or rosuvastatin and standard therapy. Lipids levels were measured at 2 weeks, 3 and 6 months. Safety of treatment was evaluated by ALT, AST, creatine kinase and HbA1c levels at baseline and at 3 and 6 months. We studied the polymorphisms of the following genes: apolipoprotein C3 (APOC3), apolipoprotein A5 (APOA5), apolipoprotein E (APOE), apolipoprotein (a) (LPA), solute carrier organic anion transporter family member 1B1 (SLCO1B1).


Reduction in lipids levels in patients with ACS was associated with T allele of rs7412 (APOE). At 6 months, carriers of TC genotype of rs662799 (APOA5) showed statistically significant decrease in triglycerides levels. Significant decrease in low-density lipoprotein (LDL) and total cholesterol was found in patients with CC/CT (rs7412, APOE) and CC/CT (rs2854117, APOC3) genotypes.


Treatment with statins resulted in a significant decrease in cholesterol levels in patients with T allele of rs7412 (APOE gene). Other SNPs had no effect of lipids concentrations. ANOVA demonstrated greater LDL-C decrease in patients with APOE and APOC3 polymorphisms.

Key words

Acute coronary syndrome, gene polymorphism, pharmacogenetics, genetics of dyslipidemias, lipids, atorvastatin, rosuvastatin.