[1]张刚,陈磊,李灵敏,等.SLCO1B1 T521C基因多态性对他汀类药物药代动力学影响的Meta分析[J].第三军医大学学报,2017,39(10):1036-1043.
 Zhang Gang,Chen Lei,Li Lingmin,et al.Influence of SLCO1B1 gene T521C polymorphism on pharmacokinetics of HMG-CoA reductase inhibitors: a meta-analysis[J].J Third Mil Med Univ,2017,39(10):1036-1043.
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SLCO1B1 T521C基因多态性对他汀类药物药代动力学影响的Meta分析(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
39卷
期数:
2017年第10期
页码:
1036-1043
栏目:
公共卫生与预防医学
出版日期:
2017-05-30

文章信息/Info

Title:
Influence of SLCO1B1 gene T521C polymorphism on pharmacokinetics of HMG-CoA reductase inhibitors: a meta-analysis
作者:
张刚陈磊李灵敏叶钧陈文生
第三军医大学西南医院全军消化病研究所
Author(s):
Zhang Gang Chen Lei Li Lingmin Ye Jun Chen Wensheng

Institute of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

关键词:
SLCO1B1OATP1B1基因多态性他汀类药物药代动力学Meta分析
Keywords:
SLCO1B1 OATP1B1 gene polymorphism statins pharmacokinetics meta-analysis
分类号:
R394.6; R969.1; R972.6
文献标志码:
A
摘要:

目的      采用Meta分析评价SLCO1B1 T521C基因多态性与他汀类药物药代动力学参数的关系。方法       计算机检索Pubmed、EMBASE、Cochrane Library、中国生物医学文献数据库、中国期刊全文数据库、万方、维普数据库,收集有关SLCO1B1 T521C基因多态性和他汀类药物药代动力学关系的研究。提取AUC0~6 h、AUC0~12 h、AUC0~24 h、AUC0-inf、Cmax和CL/F等药代动力学参数。用标准均数差(SMD)和95%CI比较野生型(TT)基因型和突变基因型(TC、CC、TC+CC)。亚组分析根据种族人群、他汀类药物的类型进行。用敏感性分析对各项研究进行异质性检验。用RevMan 5.3软件对符合纳入标准的研究进行Meta分析。结果       共纳入25篇文献903例病例,Meta分析结果显示: 全部研究的AUC0inf标准均数差TT-TC为0.51(95%CI: 0.29~0.72), TT-CC为1.80(95%CI: 1.31~2.29),TT-(TC+CC)为0.78(95%CI: 0.57~0.99);突变基因型的AUC0-inf的标准均数差较高。在白种人和亚洲人的亚组分析得出同样的结果。全部研究的Cmax标准均数差TT-TC为0.48(95%CI: 0.18~0.77),TT-CC为1.24(95%CI: 0.77~1.70), TT-(TC+CC)为0.65(95%CI: 0.43~0.87);突变基因型的Cmax的标准均数差也较高。在白种人和亚洲人的亚组分析也得出同样的结果。全部研究的CL/F标准均数差TT-TC为-1.01(95%CI: -1.91~-0.11),TT-CC为-1.51(95%CI: -2.08~-0.94),TT-(TC+CC)为-1.07(95%CI: -1.55~-0.59),突变基因型的CL/F的标准均数差较低。结论       SLCO1B1 T521C等位基因可能对他汀类药物药代动力学起着重要影响。

Abstract:

Objective      To evaluate the influence of SLCO1B1 gene T521C polymorphisms on the pharmacokinetics of statins. Methods      We searched PubMed, EMBASE, Cochrane Library, CBM, CNKI, WANFANG, and VIP databases for studies that investigated the influence of SLCO1B1 gene T521C polymorphisms on pharmacokinetics of statins. The pharmacokinetic parameters including the areas under the concentration-time curves following statin administration (AUC0~6 h, AUC0~12 h, AUC0~24 h, and AUC0-inf), the maximum plasma drug concentration (Cmax) and oral clearance (CL/F) were extracted from the included studies. The standardized mean differences (SMD) and 95% confidence intervals  (95%CI) of the pharmacokinetic parameters were calculated for comparison between subjects with TT genotype and mutant genotypes. Subgroup analyses were carried out for different ethnic populations and statin types, and sensitivity analysis was used to test the heterogeneity of the studies. Results      Twenty-five studies were eligible for analysis, including 23 published in English and 2 in Chinese involving a total of 903 subjects. Meta-analysis of the studies showed that the SWD of the AUC0-inf of the subjects with TT-TC, TT-CC, and TT-(TC+CC) genotypes was  0.51 (95%CI: 0.29~0.72), 1.80 (95%CI: 1.31~2.29) and 0.78 (95%CI: 0.57~0.99), respectively, suggesting a higher SWD of AUC0-inf in mutant genotypes than in the wild-type genotype. The same result was obtained in subgroup analysis of Caucasian and Asian populations. The SWD of Cmax in subjects with TT-TC, TT-CC, and TT-(TC+CC) genotypes was 0.48 (95%CI: 0.18~0.77), 1.24 (95%CI: 0.77~1.70) and 0.65 (95%CI: 0.43~0.87), respectively, also higher in the mutant genotypes; subgroup analysis of Caucasian and Asian populations also yielded the same result. The SWD of CL/F in the subjects with the 3 genotypes was -1.01 (95%CI: -1.91~-0.11), -1.51 (95%CI: -2.08~-0.94) and -1.07 (95%CI: -1.55~-0.59), respectively, lower in the mutant genotypes than in the wild-type genotype. Conclusion      SLCO1B1 gene T521C allele may have an important effect on the pharmacokinetics of statins.

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更新日期/Last Update: 2017-05-22