Influence of SLCO1B1 gene T521C polymorphism on pharmacokinetics of HMG-CoA reductase inhibitors: a meta-analysis

Gang Zhang; Lei Chen; Lingmin Li; Jun Ye; Wensheng Chen

doi:10.16016/j.1000-5404.201612183

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Influence of SLCO1B1 gene T521C polymorphism on pharmacokinetics of HMG-CoA reductase inhibitors: a meta-analysis

Public Health and Preventive Medicine | 更新时间：2026-02-09

- Influence of SLCO1B1 gene T521C polymorphism on pharmacokinetics of HMG-CoA reductase inhibitors: a meta-analysis
- Journal of Third Military Medical University Vol. 39, Issue 10, Pages: 1036-1043(2017)
- 作者机构：
  
  400038 重庆，第三军医大学西南医院全军消化病研究所
- 作者简介：
- 基金信息：
  
  by the General Program of National Natural Science Foundation of China(81470850)
- DOI：10.16016/j.1000-5404.201612183
  CLC： R394.6;R969.1;R972.6
- Received：21 December 2016，
  
  Revised：2017-02-21，
  
  Published：30 May 2017
- 稿件说明：
移动端阅览
Gang Zhang, Lei Chen, Lingmin Li, et al. Influence of SLCO1B1 gene T521C polymorphism on pharmacokinetics of HMG-CoA reductase inhibitors: a meta-analysis[J]. Journal of Third Military Medical University, 2017, 39(10): 1036-1043.
DOI：

Gang Zhang, Lei Chen, Lingmin Li, et al. Influence of SLCO1B1 gene T521C polymorphism on pharmacokinetics of HMG-CoA reductase inhibitors: a meta-analysis[J]. Journal of Third Military Medical University, 2017, 39(10): 1036-1043. DOI： 10.16016/j.1000-5404.201612183.

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AUC

0~6 h

、AUC

0~12 h

、AUC

0~24 h

、AUC

0-inf

、C

max

和CL/F等药代动力学参数。用标准均数差(

SMD

)和95%

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AUC

0-inf

标准均数差TT-TC为0.51(95%

: 0.29~0.72)，TT-CC为1.80(95%

: 1.31~2.29)，TT-(TC+CC)为0.78(95%

: 0.57~0.99)；突变基因型的AUC

0-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C

max

标准均数差TT-TC为0.48(95%

: 0.18~0.77)，TT-CC为1.24(95%

: 0.77~1.70)，TT-(TC+CC)为0.65(95%

: 0.43~0.87)；突变基因型的C

max

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%

: -1.91~-0.11)，TT-CC为-1.51(95%

: -2.08~-0.94)，TT-(

TC+CC)为-1.07(95%

: -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 (AUC

0~6 h

AUC

0~12 h

AUC

0~24 h

and AUC

0-inf

)

the maximum plasma drug concentration (C

max

) and oral clearance (CL/F) were extracted from the included studies. The standardized mean differences (SMD) and 95% confidence intervals (95%

) 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 AUC

0-inf

of the subjects with TT-TC

TT-CC

and TT-(TC+CC) genotypes was 0.51 (95%

: 0.29~0.72)

1.80 (95%

: 1.31~2.29) and 0.78 (95%

: 0.57~ 0.99)

respectively

suggesting a higher SWD of AUC

0-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 C

max

in subjects with TT-TC

TT-CC

and TT-(TC+CC) genotypes was 0.48

(95%

: 0.18~0.77)

1.24 (95%

: 0.77~1.70) and 0.65 (95%

: 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%

: -1.91~-0.11)

-1.51 (95%

: -2.08~-0.94) and -1.07 (95%

: -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.

关键词

Keywords

references

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