Lipid-lowering effect of fluvastatin in relation to cytochrome P450 2C9 variant alleles frequently distributed in the Czech population

Med Sci Monit. 2012 Aug;18(8):CR512-517. doi: 10.12659/msm.883272.

Abstract

Background: CYP2C9*3 allele has been reported to correlate with increased plasma concentration of fluvastatin active form in healthy volunteers. We analyzed the correlation between the CYP2C9 genotype and cholesterol-lowering effect of fluvastatin in human hypercholesterolemic patients.

Material/methods: The study was prospective, without any interventions to standard procedures of hypolipidemic treatment. CYP2C9 genotype was determined by PCR-RFLP assay in 87 patients on concomitant fluvastatin therapy, in 48 patients on monotherapy, and in a control group of 254 healthy volunteers of Czech nationality. Biochemical and clinical data were collected before the initiation of fluvastatin treatment and 12 weeks later.

Results: The frequency of CYP2C9 alleles did not differ significantly among groups of patients and volunteers. The most frequently observed allele was CYP2C9*2. Treatment with 80 mg of fluvastatin daily of 48 patients on monotherapy for 12 weeks resulted in mean low-density lipoprotein cholesterol (LDL-C) reduction by 25%, mean serum total cholesterol (TC) reduction by 21%, and mean triglyceride (TG) reduction by 28%. The CYP2C9*1/*3 genotype was associated with a decrease in LDL-C levels (by 40.0% for CYP2C9*1/*3, but only by 22.4% for CYP2C9*1/*1), and with the reduction of TC (by 28.6% in CYP2C9*1/*3 versus 20.2% in CYP2C9*1/*1).

Conclusions: In hypercholesterolemic patients, LDL-C serum concentration was decreased more significantly in fluvastatin-treated subjects bearing the CYP2C9*1/*3 genotype compared to CYP2C9*1/*1 genotype. However, due to rare occurrence of some CYP genotypes, it was impossible to report a definitive positive genotype-fluvastatin effect association.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Case-Control Studies
  • Cholesterol / blood
  • Cytochrome P-450 CYP2C9
  • Czechoslovakia
  • Demography
  • Fatty Acids, Monounsaturated / adverse effects
  • Fatty Acids, Monounsaturated / pharmacology*
  • Female
  • Fluvastatin
  • Gene Frequency / genetics*
  • Genotype
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / genetics
  • Indoles / adverse effects
  • Indoles / pharmacology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Prevalence

Substances

  • Anticholesteremic Agents
  • Fatty Acids, Monounsaturated
  • Indoles
  • Fluvastatin
  • Cholesterol
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases