Effect of Cytochrome P450 7A1 (CYP7A1) Polymorphism on Lipid Responses to Simvastatin Treatment

J Cardiovasc Pharmacol. 2020 Feb;75(2):168-173. doi: 10.1097/FJC.0000000000000774.

Abstract

Background: Identifying patients with high risk of low response to statin therapy is important for optimization of lipid-lowering therapy. Cholesterol 7α-hydroxylase, a rate-limiting enzyme encoded by cytochrome P450 7A1 (CYP7A1) gene, is considered to be associated with statin efficacy. This study aimed to investigate the association between a novel CYP7A1 single nucleotide polymorphism rs3824260 and statin treatment response for hypercholesteremic patients in Chinese Han population.

Methods: A total of 336 subjects were prescribed with simvastatin for 12 weeks after enrollment. Plasma lipid parameters were measured at enrollment and after 12-week simvastatin treatment separately. Subjects were classified into high- and low-response groups depending on their total cholesterol, low-density lipoprotein cholesterol (LDL-C) and TG changes and increase or reduction groups according to their high-density lipoprotein cholesterol (HDL-C) levels changing after simvastatin treatment. The CYP7A1 rs3824260 was genotyped from blood samples with a SNaPshot assay.

Results: At baseline, the LDL-C level and TG level were significantly higher in the AA genotype, while the HDL-C level was significantly higher in the GG genotype of CYP7A1 rs3824260. Patients carrying AA genotype are at an increased risk of low response for LDL-C reduction (odds ratio = 2.295, 95% confidence interval = 1.164-4.524, P = 0.016). Furthermore, the GG genotype of rs3824260 was significantly associated with a high risk of HDL-C reduction response after simvastatin therapy (odds ratio = 2.240, 95% confidence interval = 1.137-4.413, P = 0.025).

Conclusions: The CYP7A1 gene polymorphism rs3824260 is related to inappropriate response of simvastatin treatment for hypercholesterolemia patients in Chinese Han population.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Biomarkers / blood
  • China
  • Cholesterol 7-alpha-Hydroxylase / genetics*
  • Cholesterol 7-alpha-Hydroxylase / metabolism
  • Cholesterol, LDL / blood*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / genetics
  • Male
  • Middle Aged
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Simvastatin / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Triglycerides / blood*

Substances

  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Triglycerides
  • Simvastatin
  • CYP7A1 protein, human
  • Cholesterol 7-alpha-Hydroxylase