SLCO1B1和APOE基因多态性对瑞舒伐他汀调脂疗效及不良反应的影响

Effects of SLCO1B1/APOE gene polymorphisms on lipid-lowering efficacy and adverse reactions of rosuvastatin

目的探讨SLCO1B1和APOE基因多态性对瑞舒伐他汀临床疗效及不良反应的影响。方法回顾性分析2016年3月至2017年11月中日友好医院157例原发性高脂血症患者长期口服瑞舒伐他汀调脂,并进行SLCO1B1和APOE基因分型检测的临床资料,统计分析服药前和服药8周后血脂水平、肌酸激酶(CK)水平、肝功能、肾功能、不良反应数据。结果 SLCO1B1388A> G和521T> C的基因突变率分别为58.3%和9.2%;APOE 526C> T和388T> C的基因突变率分别为9.3%和5.7%。服药8周后,SLCO1B1 388A> G和521T> C突变型患者血清低密度脂蛋白(LDL)降低程度高于野生型患者(P=0.047和0.016),APOE526C> T突变型患者血清总胆固醇(TG)降低程度高于野生型患者,组间比较均差异显著(P=0.029)。SLCO1B1388A> G突变型患者与野生型患者相比,血清载脂蛋白A1(apoA1)含量高,apoB含量低,apoA1/apoB比值明显升高(P <0.05)。SLCO1B1 521T> C突变型CK增加人数占比显著多于野生型(89%vs. 68.2%,P <0.05)。SLCO1B1和APOE基因多态性对患者肝、肾功能无显著影响(P> 0.05)。结论 SLCO1B1 388A> G和APOE 526C> T基因多态性影响瑞舒伐他汀的调脂疗效,SLCO1B1521T> C可能与瑞舒伐他汀的不良反应相关。检测SLCO1B1和APOE基因分型有助于规避用药风险。

AIM To investigate the effects of SLCO1B1 and APOE gene polymorphisms on the clinical efficacy and adverse reactions of rosuvastatin. METHODS A retrospective analysis was carried out to analyze the clinical data of 157 patients with primary hyperlipidemia who received long-term oral administration of rosuvastatin and detected the SLCO1B1 and APOE genotyping in China-Japan Friendship Hospital from Mar. 2016 to Nov. 2017. The blood lipid levels, creatine kinase(CK) levels, liver and renal function, and adverse reaction were analyzed before and 8 weeks after administration. RESULTS The mutation rates of SLCO1B1 388A > G and 521T > C alleles were 58.3% and 9.2%, and the mutation rates of APOE 526C > T and 388T > C alleles were 9.3% and 5.7%, respectively. After 8 weeks of administration, serum low-density lipoprotein(LDL) levels of SLCO1B1 388A > G and 521T > C mutation carriers were lower than those of wild type carriers(P = 0.047 and 0.016). Serum TG levels of APOE 526C > T mutation carriers were significantly higher than those of the wild type carriers(P = 0.029). Compared with wild type patients, the serum apolipoprotein A1(apoA1) contents and apoA1/apoB were higher, apoB contents were lower in the SLCO1B1 388A > G mutation carriers(89% vs. 68.2%, P < 0.05), and much more patients had elevated CK levels in SLCO1B1 521T > C mutation carriers. SLCO1B1 and APOE gene polymorphism had no significant effect on liver and kidney function(P > 0.05). CONCLUSION SLCO1B1 388A > G and 521T > C gene polymorphisms affect the clinical effect of rosuvastatin. SLCO1B1 521T > C may be related to the adverse reactions. Analysis the SLCO1B1 and APOE genotypes may be helpful to avoid the clinical risk of rosuvastatin.