Associations between the genotypes and phenotype of CYP3A and the lipid response to simvastatin in Chinese patients with hypercholesterolemia

Pharmacogenomics. 2013 Jan;14(1):25-34. doi: 10.2217/pgs.12.181.

Abstract

Aim: This study examined the associations between the CYP3A4*1G, CYP3A4*22, CYP3A5*3 and PPARA rs4823613 A>G polymorphisms and the phenotypes of CYP3A estimated by the ratio of 6β-hydroxycortisol:cortisol in urine, and the low-density lipoprotein cholesterol response to simvastatin in Chinese patients with hypercholesterolemia.

Patients & methods: Lipid profiles were determined off treatment and after 6 weeks of treatment with simvastatin 40 mg in 273 patients.

Results: There was no significant association between the ratio of 6β-hydroxycortisol:cortisol and the low-density lipoprotein cholesterol response to simvastatin in the study subjects (r = 0.052; p = 0.455). The genetic polymorphisms examined had no significant association with this measure of CYP3A phenotype or the lipid-lowering responses to simvastatin.

Conclusion: The results of this study suggest that genetic polymorphisms in CYP3A or other regulatory genes, or the CYP3A activity itself, is unlikely to have a significant effect on the lipid-lowering responses to simvastatin in Chinese patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / metabolism
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Female
  • Genotype
  • Humans
  • Hydrocortisone / analogs & derivatives
  • Hydrocortisone / urine
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / enzymology*
  • Hypercholesterolemia / genetics
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic
  • Simvastatin / therapeutic use*
  • Triglycerides / blood

Substances

  • Cholesterol, LDL
  • Triglycerides
  • 6 beta-hydroxycortisol
  • Simvastatin
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Hydrocortisone