【摘要】 目的分析高脂血症患者细胞色素P450 3A4^*18B（CYP3A4^*18B）基因多态性对辛伐他汀稳态血药浓度及其对降脂疗效的影响。方法 115名高脂血症患者均予以辛伐他汀每次20 mg,qd,口服,连续用药4周。在治疗前和治疗后,分别抽取空腹外周静脉血2 mL,用聚合酶链反应-限制性片段长度多态性分析法分析CYP3A4^*18B的等位基因,用全自动生化分析仪测定血总胆固醇、低密度脂蛋白胆固醇等。在最后一次服药前0.5 h内,抽取外周静脉血4 mL,用HPLC法测定血中辛伐他汀的稳态药物浓度。结果 115名高血脂症患者中,CYP3A4^*18B基因型分布符合Hardy-Weinberg遗传平衡（P>0.05）,CYP3A4^*18B等位基因突变率为41.74%。CYP3A4^*1/^*1、CYP3A4^*1/^*18B和CYP3A4^*18B/^*18B的辛伐他汀稳态血药浓度分别为（4.88±0.44）,（4.90±0.38）和（4.71±0.36）ng·mL^-1,总胆固醇分别为（5.78±0.47）,（5.84±0.47）和（5.82±0.52）mmol·L^-1,低密度脂蛋白胆固醇分别为（2.63±0.04）,（2.60±0.08）和（2.58±0.12）mmol·L^-1,差异均无统计学意义（均P>0.05）。结论 CYP3A4^*18B基因多态性对辛伐他汀稳态血药浓度及降脂疗效无明显影响。更多还原

【Abstract】 Objective To investigate the frequencies of cytochrome P450 3A4^* 18B（ CYP3A4^* 18B） alleles in Chinese hyperlipidemic patients were determined,and the impact of CYP3A4^* 18B genetic polymorphism on steady plasma drug concentration and lipid lowering efficacy of simvastatin. Methods A total of 115 patients with hyperlipidemia were given 20 mg of simvastatin treatment every day for four weeks. 115 hyperlipidemic patients were respectively extracted 2 mL peripheral venous blood on an empty stomach before taking medicine and after dosing four weeks. CYP3A4^* 18B alleles were measured by polymerase chain reaction-based restriction fragment length polymorphism（ PCR-RFLP）,blood total cholesterol and low-density lipoprotein cholesterol were determined with fully automatic biochemical analyser. After dosing for four weeks,4 mL peripheral venous blood of 115 hyperlipidemic patients were collected,and the steady-state drug concentration ofsimvastatin was determined by HPLC. Results CYP3A4^* 18B genotype distribution of 115 hyperlipidemic patients accords with Hardy-Weinberg genetic balance（ P > 0. 05）,CYP3A4^* 18B allelic gene mutation rate was 41. 74%.Steady plasma simvastatin concentrations of CYP3A4^* 1/^*1,CYP3A4^* 1/^*18B and CYP3A4^* 18B/^*18B groups were（ 4. 88 ± 0. 44）,（ 4. 90 ± 0. 38） and（ 4. 71 ± 0. 36） ng·mL^-1,total cholesterols of three groups were（ 5. 78 ± 0. 47）,（ 5. 84 ± 0. 47） and（ 5. 82 ± 0. 52） mmol·L^-1,low density lipoprotein cholesterols of three groups were（ 2. 63 ± 0. 04）,（ 2. 60 ± 0. 08） and（ 2. 58 ± 0. 12） mmol·L^-1. Lipid-lowering efficacy and steady plasma drug concentration had no statistical difference between CYP3A4^* 1/^*1,CYP3A4^* 1/^*18B and CYP3A4^* 18B/^*18B groups（ P > 0. 05）. Conclusion There were no obvious effects of CYP3A4^* 18B gene polymorphism on steady state drug concentration and lipid-lowering efficacy of simvastatin in Chinese hyperlipidemic patients.更多还原