Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients

Cell Physiol Biochem. 2016;39(2):630-8. doi: 10.1159/000445654. Epub 2016 Jul 15.

Abstract

Background/aims: The aim of the present study is to investigate whether the single nucleotide polymorphism (SNP) in lipid metabolism related genes would affect the effectiveness of atorvastatin in both Han and Uighur populations.

Methods: 200 ischemic stroke patients were treated with atorvastatin. The differences of blood lipid level and their ratios were measured. Six lipid related genes, HMGCR, APOA5, LPL, CETP, LDLR and PCSK9 were selected as candidate genes. And nine SNP loci in these six genes were genotyped by SNaPshot technique.

Results: In all patients treated with atorvastatin, the SNP rs662799 significantly affected the ratio of x0394;LDL and x0394;LDL/LDL (p < 0.05); the SNP rs320 significantly affected the ratio of x0394;LDL/LDL and x0394;(LDL/HDL)/(LDL/HDL) (p < 0.01) and the SNP rs708272 significantly affected the ratio of x0394;LDL (p < 0.05). In Han population treated with atorvastatin, the SNP rs662799 significantly affected the ratio of x0394;TG (p < 0.05); the SNP rs320 significantly affected the ratio of x0394;LDL/LDL and x0394;(LDL/HDL)/(LDL/HDL) (p < 0.01). In Uighur population treated with atorvastatin, the SNP rs2266788 significantly affected the ratio of x0394;HDL (p < 0.05); the SNP rs662799 significantly affected the ratio of x0394;LDL/LDL (p < 0.05) and the SNP rs708272 significantly affected the ratio of x0394;LDL (p < 0.05).

Conclusion: Polymorphisms of rs662799 and rs2266788 in APOA5 gene, rs320 in LPL gene and rs708272 in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients.

MeSH terms

  • Aged
  • Anticholesteremic Agents / therapeutic use
  • Apolipoprotein A-V / genetics
  • Apolipoprotein A-V / metabolism
  • Atorvastatin / therapeutic use*
  • Brain Ischemia / complications
  • Cholesterol Ester Transfer Proteins / genetics
  • Cholesterol Ester Transfer Proteins / metabolism
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Lipoprotein Lipase / genetics
  • Lipoprotein Lipase / metabolism
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / metabolism
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Proprotein Convertase 9 / genetics
  • Proprotein Convertase 9 / metabolism
  • Stroke / drug therapy*
  • Stroke / etiology
  • Stroke / genetics

Substances

  • Anticholesteremic Agents
  • Apolipoprotein A-V
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Atorvastatin
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases
  • LPL protein, human
  • Lipoprotein Lipase
  • PCSK9 protein, human
  • Proprotein Convertase 9