Gender-Specific Association Between ABCC2 -24C>T SNP and Reduction in Triglycerides in Chilean Patients Treated With Atorvastatin

Basic Clin Pharmacol Toxicol. 2018 May;122(5):517-522. doi: 10.1111/bcpt.12943. Epub 2018 Jan 4.

Abstract

Statins are the first-line therapy prescribed to lower plasma cholesterol levels. Although being safe and showing several beneficial cholesterol-independent pleiotropic effects, a significant variability regarding statin's therapeutic goals has been abundantly documented, but less understood. We aimed to investigate the influence of the ABCC2 -24C>T single nucleotide polymorphism on Chilean hypercholesterolaemic individuals treated for 4 weeks with 10 mg/day atorvastatin. A total of 127 individuals medicated with atorvastatin 10 mg/day/4 weeks were included. Lipid profiles were determined before and after drug administration by conventional assays. Genotyping of the ABCC2 rs717620 SNP (-24C>T) was performed with TaqMan® Drug Metabolism Genotyping Assays. As expected, atorvastatin reduced TC, LDL-C and TG concentrations (p < 0.05). Also, HDL-C levels were increased (p < 0.05). Minor allele frequency for the rs717620 was 0.232. Overall, atorvastatin response was not associated with the ABCC2 rs717620 SNP (p > 0.05). Nonetheless, in male individuals carrying the -24T allele, we observed an attenuated reduction in both TG values and the TG/HDL-C ratio after 10 mg/day atorvastatin. This study indicates that TG levels and the TG/HDL-C ratio are affected by the rs717620 SNP in Chilean males but not female individuals after atorvastatin treatment.

MeSH terms

  • Adult
  • Aged
  • Atorvastatin / therapeutic use*
  • Biomarkers / blood
  • Chile
  • Cholesterol / blood
  • Down-Regulation
  • Female
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / genetics
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Pharmacogenetics
  • Pharmacogenomic Variants*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Sex Factors
  • Time Factors
  • Treatment Outcome
  • Triglycerides / blood*

Substances

  • ABCC2 protein, human
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Triglycerides
  • Cholesterol
  • Atorvastatin