Gao Yuan, Zhang Li-rong, Fu Qiang
Department of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, China.
Eur J Clin Pharmacol. 2008 Sep;64(9):877-82. doi: 10.1007/s00228-008-0502-x. Epub 2008 Jun 5.
Our aim was to observe the impact of CYP3A4*1G genetic polymorphism on lipid-lowering efficacy of statins.
We studied 217 unrelated hyperlipidemic patients who prospectively received atorvastatin and 199 patients who received simvastatin as a single-agent therapy (20 mg day(-1) p.o.) for 4 weeks. Genotyping of CYP3A4*1G was conducted by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were determined before and after treatment by enzymatic assays.
The frequency of CYP3A4*1G in Chinese hyperlipidemic patients was 0.276. After atorvastatin treatment, the mean percentage reduction in serum TC was 16.8 +/- 3.3% (*1/*1), 17.8 +/- 3.8% (*1/*1G), and 20.9 +/- 5.0% (1G/1G), respectively. The CYP3A41G polymorphism had a gene-dose-dependent effect on percentage reduction in serum TC (P < 0.01). Conversely, there was no significant association between lipid-lowering efficacy of simvastatin and CYP3A41G polymorphism.
Carrying CYP3A4*1G increase the lipid-lowering efficacy of atorvastatin and may have no significant effect on simvastatin treatment.
我们的目的是观察CYP3A4*1G基因多态性对他汀类药物降脂疗效的影响。
我们研究了217例前瞻性接受阿托伐他汀治疗的无亲缘关系的高脂血症患者和199例接受辛伐他汀单药治疗（口服20毫克/天）4周的患者。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析对CYP3A4*1G进行基因分型。治疗前后通过酶法测定血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平。
中国高脂血症患者中CYP3A4*1G的频率为0.276。阿托伐他汀治疗后，血清TC的平均降低百分比分别为16.8±3.3%（*1/*1）、17.8±3.8%（*1/*1G）和20.9±5.0%（1G/1G）。CYP3A41G多态性对血清TC降低百分比有基因剂量依赖性影响（P<0.01）。相反，辛伐他汀的降脂疗效与CYP3A41G多态性之间无显著关联。
携带CYP3A4*1G可提高阿托伐他汀的降脂疗效，对辛伐他汀治疗可能无显著影响。
