Department of Pharmacology, 1st Faculty of Medicine, Charles University and General Teaching Hospital, Prague, Czech Republic.
Med Sci Monit. 2012 Aug;18(8):CR512-517. doi: 10.12659/msm.883272.
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.
The frequency of CYP2C9 alleles did not differ significantly among groups of patients and volunteers. The most frequently observed allele was CYP2C92. 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 CYP2C91/3 genotype was associated with a decrease in LDL-C levels (by 40.0% for CYP2C91/3, but only by 22.4% for CYP2C91/1), and with the reduction of TC (by 28.6% in CYP2C91/3 versus 20.2% in CYP2C91/*1).
In hypercholesterolemic patients, LDL-C serum concentration was decreased more significantly in fluvastatin-treated subjects bearing the CYP2C9*1/3 genotype compared to CYP2C91/*1 genotype. However, due to rare occurrence of some CYP genotypes, it was impossible to report a definitive positive genotype-fluvastatin effect association.
CYP2C9*3 等位基因与健康志愿者中氟伐他汀活性形式的血浆浓度升高相关。我们分析了 CYP2C9 基因型与人类高脂血症患者氟伐他汀降脂作用之间的相关性。
材料/方法：该研究为前瞻性研究，不进行任何干预，采用标准的降脂治疗方案。在 87 例同时接受氟伐他汀治疗的患者、48 例单独接受氟伐他汀治疗的患者和 254 名捷克籍健康志愿者的对照组中，通过 PCR-RFLP 检测确定 CYP2C9 基因型。在开始氟伐他汀治疗前和 12 周后收集生化和临床数据。
患者组和志愿者组的 CYP2C9 等位基因频率无显著差异。最常见的等位基因为 CYP2C92。48 例单独接受氟伐他汀治疗的患者每天服用 80mg 氟伐他汀治疗 12 周后，平均低密度脂蛋白胆固醇（LDL-C）降低 25%，总胆固醇（TC）降低 21%，甘油三酯（TG）降低 28%。CYP2C91/3 基因型与 LDL-C 水平降低相关（CYP2C91/3 降低 40.0%，而 CYP2C91/1 降低 22.4%），与 TC 降低相关（CYP2C91/3 降低 28.6%，而 CYP2C91/*1 降低 20.2%）。
在高脂血症患者中，与 CYP2C9*1/1 基因型相比，携带 CYP2C91/*3 基因型的氟伐他汀治疗患者的 LDL-C 血清浓度降低更为显著。然而，由于某些 CYP 基因型的罕见发生，无法报告明确的阳性基因型-氟伐他汀效应关联。
