缺血性脑卒中患者SLCO1B1和ApoE基因多态性对阿托伐他汀疗效和安全性的影响

Effect of SLCO1B1 and ApoE gene polymorphisms on the efficacy and safety of atorvastatin in patients with ischemic stroke

目的:分析缺血性脑卒中患者SLCO1B1和ApoE基因的分布情况,探讨其单核苷酸多态性(SNPs)对阿托伐他汀降脂疗效和安全性的影响。方法:选择2018年1-12月某院收治的160例缺血性脑卒中患者,应用PCR荧光探针法对患者SLCO1B1基因的388A>G、521T>C位点和ApoE基因的526C>T、 388T>C位点的多态性进行检测。入选患者均口服阿托伐他汀20 mg·d-1,通过检测用药前及用药后30 d患者的总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白(HDL-C)水平,评价阿托伐他汀的降脂疗效;通过检测用药前及用药后30 d患者血清肌酐(Cr)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酸激酶(CK)水平,评价阿托伐他汀的安全性。结果:缺血性脑卒中患者SLCO1B1 388A>G和521T>C等位基因频率分别为73.75%和10.62%,ApoE基因的e2、e3和e4等位基因频率分别为7.50%、80.00%和12.50%,各基因型符合Hardy-Weinberg平衡定律。SLCO1B1(TC+CC)组患者给药30 d后LDL-C明显降低,CK明显升高,与TT组差异有统计学意义(P<0.05)。SLCO1B1 388A>G和ApoE SNPs对降脂疗效和安全性的差异无统计学意义(P>0.05)。结论:SLCO1B1 521C等位基因增强阿托伐他汀的降脂作用,尤其对LDL-C效果明显,但会增加肌病的风险。ApoE SNPs对阿托伐他汀的降脂疗效及安全性无显著影响。

OBJECTIVE To analyze the distribution of SLCO1 B1 and ApoE gene polymorphisms in patients with ischemic stroke,and to explore the effect of the single nucleotide polymorphisms(SNPs)on the efficacy and safety of atorvastatin in lipid-lowering patients.METHODS 160 patients with ischemic stroke admitted to our hospital from January 2018 to December 2018 were selected.The genetic polymorphisms of SLCO1 B1 388 A>G and 521 T>C and 526 C>T,388 T>C were performed by PCR detection,and analyze its genotype distribution.The eligible patients were given oral atorvastatin 20 mg,qd,and the levels of the total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol of the patient before and after treatment were measured to evaluate the efficacy of lipid-lowering of ATV.The safety of atorvastatin was evaluated through detecting serum creatinine(Cr),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatine kinase(CK)levels.RESULTS The allele frequencies of SLCO1 B1 388 A>G and 521 T>C in ischemic stroke patients were 73.75% and 10.62%,respectively.The e2,e3,and e4 allele frequencies of the ApoE gene were 7.50%,80.00%,and 12.50%,respectively.The distribution of the gene polymorphisms was in Hardy-Weinberg equilibrium.After oral intake of atorvastatin 20 mg daily for 30 d,LDL-C was significantly decreased in patients with SLCO1 B1(TC+CC)group,CK was significantly increased,and the difference was statistically significant compared with TT group(P<0.05).There was no significant difference in the efficacy and safety of SLCO1 B1 388 A>G and ApoE SNPs(P>0.05).CONCLUSION The SLCO1 B1 521 C allele could enhance the lipid lowering effect of atorvastatin,especially on LDL-C,but increases the risk of myopathy.No significant impact of ApoE SNPs on the lipid-lowering efficacy and safety of atorvastatin has been found.