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Meta-analysis of effects of ABCB1 polymorphisms on clopidogrel response among patients with coronary artery disease

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The substantial variability in the antiplatelet efficacy of clopidogrel has raised major concerns. Molecular epidemiological research suggests that ABCB1 C3435T polymorphism may be associated with clopidogrel response, but results remain controversial. To derive a more precise evaluation of the associations between ABCB1 C3435T polymorphism and the clinical efficacy of clopidogrel, we have conducted a PRISMA-compliant meta-analysis.

Methods

The PubMed and EMBASE databases were searched for eligible studies up to 25 October 2016. The odds ratio (OR), the standard mean difference (SMD) and 95% confidence interval (CI) were applied to assess the strength of the relationship.

Results

Overall, 28 related studies involving 23,243 patients were analyzed. No association was found between the ABCB1 polymorphisms and the primary outcome. In the subgroup analysis, the C3435T mutation significantly reduced platelet activity as tested by the LTA assay in the dominant (SMD −0.140, 95% CI −0.272 to −0.009, P = 0.036) and heterozygous (SMD −0.154, 95% CI −0.290 to −0.017, P = 0.027) models, but the result lacked robustness in the sensitivity analysis. A significant association between the C3435T polymorphism and bleeding risk was also observed with low heterogeneity in the dominant (OR 1.805, 95% CI1.124–2.900, P =0.015, I 2 = 0%), homozygous (OR 1.952, 95% CI 1.055–3.611, P = 0.033, I 2 = 13.2%) and heterozygous (OR 1.793, 95% CI 1.091–2.946, P = 0.021, I 2 = 0%) models in Asian patients.

Conclusions

The results of the meta-analysis suggest that ABCB1 C3435T polymorphism may increase the risk of bleeding in Asian patients treated with clopidogrel. The implied relationship needs to be verified in future basic genetic pharmacology studies.

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Acknowledgments

This work was supported by the National Social Science Foundation of China (no. 16BGL183), the Natural Science Foundation of Shaanxi Province (no. 2015JM8415) and the Fundamental Research Funds for the Central Universities of China (no. 2011jdhz55). 

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  1. Yajing Zhai and Hairong He contributed equally to this work

Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China

    Yajing Zhai, Jiao Xie, Ti Meng & Yalin Dong

  2. Clinical Research Center, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China

    Hairong He, Xiancang Ma & Jun Lu

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  1. Yajing Zhai
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Contributions

Yajing Zhai and Hairong He contributed equally to this work. Yalin Dong and Jun Lu designed the research. Yajing Zhai, Hairong He and Jun Lu executed the analysis, interpreted the findings and revised the first and subsequent drafts of the manuscript. Yalin Dong, Xiancang Ma, Jiao Xie, and Ti Meng contributed to data analysis, interpretation of findings and manuscript preparation. All authors approved the final version.

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Correspondence to Yalin Dong or Jun Lu.

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Zhai, Y., He, H., Ma, X. et al. Meta-analysis of effects of ABCB1 polymorphisms on clopidogrel response among patients with coronary artery disease. Eur J Clin Pharmacol 73, 843–854 (2017). https://doi.org/10.1007/s00228-017-2235-1

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