SLCO1B1基因多态性对瑞舒伐他汀有效性和安全性影响的Meta分析  

Meta-analysis of the effects of SLCO1B1 gene polymorphisms on the efficacy and safety of rosuvastatin

作　　者：鲁春云 王松[1] 刘克锋[1] 薛莹 陈娟娟[1] 赵院霞[1] 杜书章[1] LU Chunyun;WANG Song;LIU Kefeng;XUE Ying;CHEN Juanjuan;ZHAO Yuanxia;DU Shuzhang(Dept.of Pharmacy,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院药学部,郑州450052

出　　处：《中国药房》2024年第19期2397-2403,共7页China Pharmacy

基　　金：河南省重点研发与推广专项(科技攻关)项目(No.232102311200)。

摘　　要：目的 研究SLCO1B1基因(521T>C和388A>G)多态性与瑞舒伐他汀有效性和安全性的相关性。方法 在PubMed、Embase、Cochrane Library、PharmGKB、中国知网和万方数据库中检索521T>C和388A>G基因多态性对瑞舒伐他汀有效性和安全性影响的研究,检索时限为建库起至2023年12月,用RevMan 5.3软件对所纳入的数据进行分析。结果 共纳入16篇相关研究。Meta分析结果显示,521T>C基因多态性与瑞舒伐他汀疗效有显著相关性——在显性基因模型下,与TT基因型相比,CC+TC基因型能显著提高瑞舒伐他汀升高高密度脂蛋白胆固醇(HDL-C)的疗效[MD=2.38,95%CI(0.61,4.16),P=0.009 0];在纯合子基因模型下,与TT基因型相比,CC基因型能显著提高瑞舒伐他汀降低总胆固醇的疗效[MD=-7.50,95%CI(-13.05,-1.95),P=0.008 0];在杂合子基因模型下,与TT基因型相比,TC基因型能显著提高瑞舒伐他汀降低低密度脂蛋白胆固醇(LDL-C)[MD=-5.14,95%CI(-9.74,-0.53),P=0.03]和升高HDL-C[MD=5.67,95%CI(2.61,8.73),P=0.000 3]的疗效。388A>G基因多态性与瑞舒伐他汀疗效亦有显著相关性——在显性或纯合子基因模型下,与AA基因型相比,GG+AG基因型[MD=-6.88,95%CI(-7.46,-6.30),P<0.000 1]或GG基因型[MD=-9.23,95%CI(-9.41,-9.04),P<0.000 1]能显著提高瑞舒伐他汀降低LDL-C的疗效;在杂合子基因模型下,与AA基因型相比,AG基因型能显著提高瑞舒伐他汀降低LDL-C[MD=-3.00,95%CI(-3.19,-2.82),P<0.000 1]、总胆固醇[MD=-5.80,95%CI(-6.00,-5.59),P<0.000 1]和甘油三酯[MD=-11.79,95%CI(-19.57,-4.02),P=0.003 0]的疗效;在隐性基因模型下,与AA+AG基因型相比,GG基因型能显著提高瑞舒伐他汀降低LDL-C[MD=-4.31,95%CI(-8.47,-0.14),P=0.040 0]和升高HDL-C[MD=4.49,95%CI(2.20,6.77),P=0.000 1]的疗效。4种基因模型下,521T>C基因多态性与瑞舒伐他汀相关ADR发生概率之间均存在显著相关性(P<0.05),但并未发现388A>G基因多态性与瑞舒伐他汀相关ADR发生概率之间存在显著相关性(P>0.OBJECTIVE To study the correlation between SLCO1B1(521T>C and 388A>G)gene polymorphisms and the efficacy and safety of rosuvastatin.METHODS Retrieved from PubMed,Embase,Cochrane Library,PharmGKB,CNKI database and Wanfang database,the studies about the effects of 521T>C and 388A>G gene polymorphisms on the efficacy and safety of rosuvastatin were collected during the inception to Dec.2023.The included data were analyzed by using RevMan 5.3 software.RESULTS A total of 16 studies were included.The results of meta-analysis showed that 521T>C gene polymorphism was significantly correlated with the efficacy of rosuvastatin.In the dominant gene model,compared with TT genotype,CC+TC genotype significantly improved the efficacy of rosuvastatin in raising high-density lipoprotein cholesterol(HDL-C)[MD=2.38,95%CI(0.61,4.16),P=0.0090].In the homozygous gene model,compared with TT genotype,CC genotype significantly improved the efficacy of rosuvastatin in reducing total cholesterol[MD=-7.50,95%CI(-13.05,-1.95),P=0.0080].In heterozygous gene model,compared with TT genotype,TC genotype significantly improved rosuvastatin in reducing low-density lipoprotein cholesterol(LDL-C)[MD=-5.14,95%CI(-9.74,-0.53),P=0.03]and increasing HDL-C[MD=5.67,95%CI(2.61,8.73),P=0.0003].388A>G gene polymorphism was also significantly correlated with the efficacy of rosuvastatin.In dominant or homozygous gene models,compared with AA genotype,GG+AG genotype[MD=-6.88,95%CI(-7.46,-6.30),P<0.0001]or GG genotype[MD=-9.23,95%CI(-9.41,9.04),P<0.0001]significantly improved the efficacy of rosuvastatin in lowering LDL-C.In the heterozygous gene model,compared with AA genotype,AG genotype significantly improved the efficacy of rosuvastatin in lowering LDL-C[MD=-3.00,95%CI(-3.19,-2.82),P<0.0001],total cholesterol[MD=-5.80,95%CI(-6.00,-5.59),P<0.0001]and triglyceride[MD=-11.79,95%CI(-19.57,-4.02),P=0.0030].In the recessive gene model,compared with AA+AG genotype,GG genotype significantly improved the therapeutic efficacy of rosuvastatin in reducing LDL-C[MD=-4.31

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

分 类 号：R969[医药卫生—药理学] R972[医药卫生—药学]