SLCO1B1(521T>C和388A>G)基因多态性对阿托伐他汀有效性和安全性影响的Meta分析  

Meta-analysis of the SLCO1B1(521T>C and 388A>G)gene polymorphisms on the efficacy and safety of atorvastatin

作　　者：鲁春云 刘克锋[1] 王松[1] 杜书章[1] LU Chunyun;LIU Kefeng;WANG Song;DU Shuzhang(Department of Pharmacy,the First Affiliated Hospital of Zhengzhou University,Henan Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院药学部,河南郑州450052

出　　处：《中国医院药学杂志》2023年第22期2529-2538,共10页Chinese Journal of Hospital Pharmacy

摘　　要：目的:系统评价SLCO1B1(521T>C和388A>G)基因多态性对阿托伐他汀有效性和安全性的影响,为临床个体化用药提供循证参考。方法:计算机检索PubMed、Embase、Cochrane Library、pharmGKB、CNKI数据库和万方数据库,检索时限均为建库起至2023年3月。收集521T>C和388A>G基因多态性对阿托伐他汀有效性和安全性影响的研究,用Rev Man 5.3软件进行Meta分析。结果:共纳入24篇(中文9篇,英文15篇)相关研究,共计6719例研究对象。其中,涉及521T>C的研究为23项,涉及388A>G的研究为11项。Meta分析结果显示:521T>C基因多态性与阿托伐他汀疗效无相关性,在4种基因模型下,用药前后LDL-C、TC、TG和HDL-C变化率差异均无统计学意义(P>0.05)。521T>C基因多态性与阿托伐他汀相关的不良反应(ADR)有显著相关性[显性基因模型(OR=1.44,95%CI:1.15~1.80,P=0.001)和杂合子基因模型(OR=1.73,95%CI:1.21~2.48,P=0.003)]。4种基因模型下,均未发现388A>G基因多态性与用药前后LDL-C、TC、TG、HDL-C变化率和阿托伐他汀相关的ADR之间存在显著相关性(P>0.05)。结论:521T>C基因多态性与阿托伐他汀降脂疗效无显著相关性,但与阿托伐他汀安全性显著相关,C等位基因可能是导致阿托伐他汀ADR增多的因素之一;388A>G基因多态性与阿托伐他汀降脂疗效和安全性之间均无关联性。OBJECTIVE To systematically evaluate the effects of SLCO1B1(521T>C and 388A>G)gene polymorphisms on the efficacy and safety of atorvastatin,so as to provide evidence-based reference for clinical individualized drug use.METHODS PubMed,Embase,Cochrane Library,pharmGKB,CNKI database and Wanfang database were searched by computer from the establishment of the database to March 2023.Studies on the effects of 521T>C and 388A>G gene polymorphisms on the efficacy and safety of atorvastatinwere collected,and Meta-analysis was performed using Rev Man 5.3 software.RESULTS A total of 24 studies(9 in Chinese and 15 in English)were included,with a total of 6719 subjects.Among them,23 studies involved 521T>C and 11 studies involved 388A>G.The results of Meta-analysis showed that:There was no correlation between the 521T>C gene polymorphism and the efficacy of atorvastatin,and there was no statistical significance in the change rates of LDL-C,TC,TG and HDL-C before and after treatment under the four gene models(P>0.05).There was a significant correlation between 521T>C gene polymorphism and atorvastatin related ADRs under dominant gene model(OR=1.44,95%CI:1.15-1.80,P=0.001)and heterozygous gene model(OR=1.73,95%CI:1.21-2.48,P=0.003).No significant correlation was found between 388A>G gene polymorphism and the change rates of LDL-C,TC,TG,HDL-C and atorvastatin related ADRs under the four gene models(P>0.05).CONCLUSION The polymorphism of 521T>C gene was not significantly correlated with the lipid-lowering effect of atorvastatin,but was significantly correlated with the safety of atorvastatin.The C allele may be one of the factors leading to the increase of ADR of atorvastatin.There was no association between 388A>G gene polymorphism and the lipid-lowering efficacy or safety of atorvastatin.

关 键 词：SLCO1B1基因多态性 阿托伐他汀 有效性 安全性 META分析 

分 类 号：R969[医药卫生—药理学]