缺血性脑卒中患者APOE和SLCO1B1基因多态性对阿托伐他汀降脂疗效和安全性的影响OA
Effects of APOE and SLCO1B1 gene polymorphisms on lipid-lowering efficacy and safety of Atorvastatin in patients with ischemic stroke
目的 分析缺血性脑卒中(IS)患者APOE和SLCO1B1基因多态性的分布特征及其对阿托伐他汀降脂疗效、安全性及IS预后的影响.方法 筛选接受阿托伐他汀降脂治疗及APOE和SLCO1B1基因分型检测的IS患者,回顾性收集临床信息,分析APOE和SLCO1B1基因多态性与IS严重程度、合并症发生风险、血脂达标率、肝功能和肌酸激酶(CK)升高率以及IS复发再入院风险的相关性.结果 研究共纳入498例使用阿托伐他汀降脂治疗的IS患者,APOE 526和388位点、SLCO1B1 388和521位点的最小等位基因频率分别为7.43%,7.93%,28.61%和10.34%,其分布均符合Hardy-Weinberg平衡(P>0.05).各位点不同基因型、等位基因、二倍体型组的中重度IS、高血压、糖尿病和冠心病发生率未见显著差异(P>0.05).APOE 526位点基因型和二倍体型对总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL)达标率影响显著(P<0.05),388位点基因型对TC达标率影响显著(P=0.017).SLCO1B1 521位点基因型和二倍体型对ALT升高率影响显著(P<0.05),388位点基因型和二倍体型对CK升高率影响显著(P<0.05).多变量Logistic回归分析显示,性别(OR=1.80,P=0.036)、年龄(OR=0.97,P=0.003)和合并高血压(OR=2.04,P=0.047)是1年内IS复发再入院风险的独立影响因素.结论 APOE基因多态性显著影响阿托伐他汀降脂疗效,SLCO1B1基因多态性显著影响阿托伐他汀安全性,在IS患者的个体化治疗中具有重要的潜在应用价值.
Objective To investigate the distribution of APOE and SLCO1B1 gene polymorphisms in ischemic stroke(IS)patients and their effects on the lipid-lowering efficacy and safety of Atorvastatin and the prognosis of IS patients.Methods The clinical data of IS patients who received lipid-lowering treatment with Atorvastatin,and APOE and SLCO1B1 genotyping were retrospectively collected.The associations between APOE and SLCO1B1 gene polymorphisms and the severity of IS,the risk of comorbidity occurrence,the rate of achieving lipid targets,the rates of increased liver function and creatine kinase(CK),and the risk of re-admission due to IS recurrence were analyzed.Results A total of 498 IS patients treated with Atorvastatin for lipid-lowering therapy were included in this study.The minor allele frequencies of APOE 526 and 388 loci,and SLCO1B1 388 and 521 loci were 7.43%,7.93%,28.61%,and 10.34%,respectively,and their distributions were in Hardy-Weinberg equilibrium(P>0.05).No significant differences were observed in the incidences of moderate to severe IS,hypertension,diabetes,and coronary heart disease among different genotypes,alleles,and haplotypes at each locus(P>0.05).The APOE 526 locus genotypes and diplotypes had significant effects on the target achievement rates of total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL)(P<0.05),and the 388 locus genotype significantly affected the rate of achieving TC target(P=0.017).The SLCO1B1 521 locus genotypes and diplotypes had significant effects on the rate of ALT elevation(P<0.05),and the 388 locus genotypes and diplotypes had significant effects on the rate of CK elevation(P<0.05).Multivariate Logistic regression analysis showed that gender(OR=1.80,P=0.036),age(OR=0.97,P=0.003),and comorbid hypertension(OR=2.04,P=0.047)were independent factors influencing the risk of re-admission due to IS recurrence within one year.Conclusion APOE gene polymorphisms significantly affect the lipid-lowering efficacy of Atorvastatin.SLCO1B1 gene polymorphisms significantly affect the safety of Atorvastatin.APOE and SLCO1B1 gene polymorphisms have important potential application value in the individualized treatment of IS patients.
刘亮;赵丹琪;王淑梅
首都医科大学附属北京世纪坛医院药学部,北京 100038首都医科大学佑安医院药学部首都医科大学附属北京世纪坛医院药学部,北京 100038
医药卫生
缺血性脑卒中ApoESLCO1B1基因多态性阿托伐他汀
ischemic strokeApoESLCO1B1gene polymorphismsAtorvastatin
《山西医科大学学报》 2026 (2)
207-214,8
国家自然科学基金资助项目(81872926)
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