Lack of association between SLCO1B1 polymorphisms and lipid-lowering response to simvastatin therapy in Thai hypercholesterolaemic patients

J Clin Pharm Ther. 2018 Oct;43(5):647-655. doi: 10.1111/jcpt.12682. Epub 2018 Mar 25.

Abstract

What is known: SLCO1B1 polymorphisms have been reported to affect the responses to statin therapy. However, the association of these polymorphisms and lipid-lowering responses has been inconsistent.

Objective: To investigate the effect of SLCO1B1 c.388A>G, c.521T>C and g.89595T>C polymorphisms on the lipid-lowering response to simvastatin therapy in Thai hypercholesterolaemic patients.

Methods: Three hundred and 91 hypercholesterolaemic patients in Southern Thailand were enrolled and treated with simvastatin 20 or 40 mg per day. Among them, 191 and 200 patients were treated for 3 and 12 months, respectively. Serum lipids were measured before and after the treatment. SLCO1B1 c.388A>G, c.521T>C and g.89595T>C polymorphisms were analysed using polymerase chain reaction-high-resolution melting (PCR-HRM).

Results: The allele frequencies of the SLCO1B1 c.388A>G, c.521T>C and g.89595T>C polymorphisms in Thai hypercholesterolaemic patients were 74.9%, 11.8% and 37.2%, respectively. After treatment with 20-40 mg simvastatin daily for 3 and 12 months, TC, TG and LDL-C concentrations were significantly lower than at baseline (P < .05). However, there was no a significant change in serum HDL-C after simvastatin treatment for 3 and 12 months (P > .05). Moreover, there was no association between SLCO1B1 c.388A>G, c.521T>C and g.89595T>C polymorphisms and lipid-lowering response to 3 and 12 months of either 20 or 40 mg/day simvastatin treatment.

What is new and conclusion: SLCO1B1 c.388A>G, c.521T>C and g.89595T>C polymorphisms may not be useful as genetic markers of lipid-lowering response to simvastatin therapy in Thai hypercholesterolaemic patients.

Keywords: SLCO1B1; hypercholesterolaemia; polymorphisms; response; simvastatin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Biomarkers / blood
  • Female
  • Gene Frequency / genetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / genetics*
  • Lipids / blood*
  • Liver-Specific Organic Anion Transporter 1 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Simvastatin / therapeutic use*
  • Thailand

Substances

  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Liver-Specific Organic Anion Transporter 1
  • SLCO1B1 protein, human
  • Simvastatin