SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization

Pharmacogenomics. 2015;16(5):449-58. doi: 10.2217/pgs.15.2.

Abstract

Aim: SLCO1B1 variants are associated with intermediate outcomes that may increase risk of death/myocardial infarction (MI) in statin-treated patients.

Patients & methods: In high-risk Caucasians undergoing cardiac catheterization, we tested the association between rs4149056/625T>C and rs2306283/492A>G with low-density lipoprotein cholesterol (LDL-c) over 3 years (n = 1402) and death/MI over 6 years (n = 2994), accounting for statin use or type during follow-up.

Results: Carriers of the rs4149056 C allele had 6.2 ± 1.7 mg/dl higher LDL-c per C allele (p < 0.001) but were not at higher risk for death/MI (p = 0.9). We found no associations between rs2306283 and LDL-c or death/MI (p > 0.6).

Conclusion: Functional SLCO1B1 variants are not associated with death/MI in patients commonly treated with statins, despite higher LDL-c in carriers of the rs4149056 C allele.

Keywords: SLCO1B1; cardiovascular events; low-density lipoprotein cholesterol; myocardial infarction; pharmacogenetics; rs2306283; rs4149056; statin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cardiac Catheterization / adverse effects*
  • Cholesterol, LDL / blood*
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / genetics
  • Myocardial Infarction / mortality
  • Organic Anion Transporters / genetics*
  • Registries
  • Survival Analysis
  • Treatment Outcome

Substances

  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human