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01 August 2012

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

Helena BuzkovaABCDEFG, Kristina PechandovaBF, Vilem DanzigB, Tomas VarekaB, Frantisek PerlikADEG, Ales ZakD, Ondrej SlanarACDEFG

DOI: 10.12659/MSM.883272

Med Sci Monit 2012; 18(8): CR512-517

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.

Keywords: Genotype, Gene Frequency - genetics, Fatty Acids, Monounsaturated - pharmacology, Demography, Czechoslovakia, Cholesterol - blood, Case-Control Studies, Aryl Hydrocarbon Hydroxylases - genetics, Anticholesteremic Agents - pharmacology, Alleles, Aged, 80 and over, Hypercholesterolemia - genetics, Indoles - pharmacology, Polymorphism, Single Nucleotide - genetics, Prevalence

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Medical Science Monitor eISSN: 1643-3750