The association between the SLCO1B1, apolipoprotein E, and CYP2C9 genes and lipid response to fluvastatin: a meta-analysis

Pharmacogenet Genomics. 2018 Dec;28(12):261-267. doi: 10.1097/FPC.0000000000000356.

Abstract

Objective: The aim of this study was to determine the impact of the SLCO1B1, apolipoprotein E (ApoE), and CYP2C9 genotypes on the lipid-lowering efficacy of fluvastatin.

Methods: We performed electronic searches on the PubMed, Embase, and Cochrane Library databases to identify studies published through October 2017. Studies that reported the effect estimates with 95% confidence intervals (CIs) of total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein were included so that the different genotype categories could be compared. Weighted mean difference (WMD) was used to summarize the effect estimates.

Results: Six studies, involving a total of 1171 individuals, were included in the final analysis. We noted that the patient carrier SLCO1B1 521TT was associated with greater change in TC (WMD: -2.98; 95% CI: -5.12 to -0.84; P=0.006) and LDL (WMD: -5.58; 95% CI: -10.64 to -0.52; P=0.031) compared with 521TC or CC. Furthermore, the patient carrier ApoE*2/*3 showed more change in high-density lipoprotein compared with ApoE*3/*3 (WMD: 18.76; 95% CI: 8.97-28.55; P<0.001) and ApoE*3/*4 or *4/*4 (WMD: 22.51; 95% CI: 0.98-44.04; P=0.040). Finally, the CYP2C9 genotypes showed no correlation with the effects of fluvastatin on TC, triglyceride, and LDL.

Conclusion: The findings of this study suggested that the SLCO1B1 and ApoE polymorphisms could influence the lipid-lowering effect of fluvastatin, whereas the CYP2C9 genotypes were not associated with the therapeutic effects of fluvastatin.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins E / genetics*
  • Biomarkers, Pharmacological / blood
  • Cholesterol / blood
  • Cholesterol / genetics
  • Cytochrome P-450 CYP2C9 / genetics*
  • Fluvastatin / administration & dosage*
  • Fluvastatin / adverse effects
  • Genetic Association Studies
  • Genotype
  • Humans
  • Lipids / blood*
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / genetics
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / genetics
  • Liver-Specific Organic Anion Transporter 1 / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Triglycerides / blood
  • Triglycerides / genetics

Substances

  • Apolipoproteins E
  • Biomarkers, Pharmacological
  • Lipids
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Liver-Specific Organic Anion Transporter 1
  • SLCO1B1 protein, human
  • Triglycerides
  • Fluvastatin
  • Cholesterol
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9