SLCO1B1和APOE基因多态性对瑞舒伐他汀疗效及安全性的影响

Effects of SLCO1B1 and APOE gene polymorphisms on therapeutic efficacy and safety of rosuvastatin

目的 探讨SLCO1B1和APOE基因多态性对瑞舒伐他汀疗效及安全性的影响。方法 入选2020年10月至2021年10月服用瑞舒伐他汀的冠心病患者300例,根据瑞舒伐他汀服用剂量分为10 mg组及20 mg组,每组150例。检测患者SLCO1B1和APOE基因型,监测患者用药前、用药1、3和6个月后的血脂水平指标,并随访其6个月内肌肉、肝脏和神经系统等不良反应发生情况。结果 SLCO1B1 388A>G、521T>C与APOE 526C>T、388T>C的突变率分别为71.7%、13.8%、7.8%和10.5%。20 mg组中,携带SLCO1B1 521T>C突变或*15突变的患者的肌肉不良反应发生率高于非携带者(P<0.05),但在10 mg组中差异无统计学意义(P> 0.05)。在全部患者组中,携带APOE 526C>T突变患者总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)降低水平显著高于野生型患者(P <0.05),携带APOE 388T>C突变患者TC及LDL-C降低水平显著低于野生型患者(P <0.05),在10 mg组中仅携带APOE 388T>C突变患者LDL-C降低水平显著低于野生型患者(P <0.05),20 mg组中比较差异均无统计学意义(P> 0.05)。结论 SLCO1B1 521T>C突变增加了瑞舒伐他汀的肌肉不良反应发生率,APOE 526C>T突变增强了瑞舒伐他汀降脂作用,APOE 388T>C突变减弱了瑞舒伐他汀降脂作用。SLCO1B1基因多态性对瑞舒伐他汀安全性的影响在20 mg组更显著,APOE基因多态性对瑞舒伐他汀疗效的影响在10 mg组更显著。

Objective To investigate the effects of SLCO1B1 and APOE gene polymorphisms on therapeutic efficacy and safety of rosuvastatin in patients with coronary heart disease(CHD). Methods A total of 300 patients with CHD took rosuvastatin from October 2020 to October 2021 were enrolled in. The patients were assigned to 10 mg group and 20 mg group depending on the dosage of rosuvastatin(10 mg/d or 20 mg/d),with 150 patients in each group. The SLCO1B1 and APOE genotypes were detected after admission. The levels of blood lipid were measured before,1 month,3 months and 6 months after administration. The adverse reactions of muscle,liver,and nervous systems were followed up for 6 months. Results The mutation rates of SLCO1B1 388 A > G,SLCO1B1 521 T > C,APOE 526 C > T,and APOE 388 T > C were 71. 7%,13. 8%,7. 8% and 10. 5%,respectively. In the 20 mg group,the incidence of muscle adverse reactions was significantly higher in patients carrying SLCO1B1 521 T > C or *15 mutation than in the non-carriers(P < 0. 05),but there was no statistical significance in the 10 mg group(P > 0. 05). In the whole patients,the reducted levels of total cholesterol(TC)and low density lipoprotein cholesterol(LDL-C)in patients carrying APOE 526 C > T mutation was significantly higher than that in wild-type patients(P < 0. 05),the reducted levels of TC and LDL-C in patients carrying APOE 388 T > C mutation was significantly lower than that in wild-type patients(P < 0. 05). However,the reducted percentage of LDL-C in patients carrying APOE 388 T > C mutation was significantly lower than that in wild-type patients(P < 0. 05)only in the 10 mg group,and there was no statistical significance in the 20 mg group(P > 0. 05). Conclusion The SLCO1B1 521 T > C mutation increased the incidence of muscle adverse reactions of rosuvastatin,APOE 526 C > T mutation enhanced the lipid-lowering effect of rosuvastatin,APOE388 T > C mutation attenuated the lipid-lowering effect of rosuvastatin. The effect of SLCO1B1 gene polymorphism on the safety of rosuvastatin was more significant in the 20 mg group,and the effect of APOE gene polymorphism on the efficacy of rosuvastatin was more significant in the 10 mg group.