MDR1C3435T基因多态性对辛伐他汀稳态血药浓度及降脂疗效的影响

Effects of MDR1C3435T gene polymorphism on steady plasma drug concentration and lipid lowering efficacy of simvastatin in Chinese hyperlipidemic patients

目的:研究高脂血症患者MDR1C3435T基因分布及其基因多态性对辛伐他汀稳态血药浓度及降脂疗效的影响。方法:115名高脂血症患者均给予每天20 mg的辛伐他汀治疗4周,在给药前及给药4周后取血样,采用PCR-RFLP(聚合酶链反应-限制性片段长度多态性分析)基因检测技术对MDR1C3435T等位基因进行分析,应用全自动生化分析仪和高效液相色谱仪分别测定血脂及辛伐他汀稳态血药浓度。结果:115名高脂血症患者MDR1C3435T基因型分布符合Hardy-Weinberg遗传平衡(P>0.05),MDR1C3435T等位基因突变率为40.87%。野生纯合子基因(CC)型组、突变杂合子(CT)型组、突变纯合子(TT)型组之间辛伐他汀稳态血药浓度及降脂疗效无统计学差异(P>0.05)。结论:未发现MDR1C3435T基因多态性对辛伐他汀稳态血药浓度及降脂疗效有明显影响。

OBJECTIVE To determine frequencies of MDR1C3435 T alleles in Chinese hyperlipidemic patients,impact of MDR1C3435 Tgenetic polymorphism on steady plasma drug concentration and lipid lowering efficacy of simvastatin.METHODS Totally 115 patients with hyperlipidemia were given 20 mg of simvastatin every day for four weeks,peripheral venous blood samples were collected before taking medicine and after dosing four weeks.MDR1C3435 Talleles were measured by PCR based restriction fragment length polymorphism（PCR-RFLP）.Contents of cholesterol and simvastatin in the blood were determined respectively by fully automatic biochemical analyzer and HPLC.RESULTS MDR1C3435 Tgenotype distribution of 115 hyperlipidemic patients were accordant with Hardy-Weinberg genetic balance（P〉0.05）.MDR1C3435 Tallelic gene mutation rate was 40.87%.Lipid lowering efficacy and steady plasma drug concentration were not significantly different between CC,CTand TT genotype groups（P〉0.05）.CONCLUSION MDR1C3435 T gene polymorphism shows no obvious effect on steady drug concentration and lipid lowering efficacy of simvastatin in Chinese hyperlipidemic patients.