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Two common mutations within CYP2C19 affected platelet aggregation in Chinese patients undergoing PCI: a one-year follow-up study

The Pharmacogenomics Journal volume 19, pages 157–163 (2019)Cite this article

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Abstract

The effect of dual antiplatelet therapy, clopidogrel combined with aspirin, was influenced by CYP2C19 gene mutation and heterogeneity of population. Related studies remained controversial and limited, especially in Chinese. Total 3295 unrelated ACS Chinese patients undergoing percutaneous coronary intervention (PCI) were recruited and followed up to 1 year. Meanwhile, baseline and clinical data were retrieved. CYP2C19*2 and *3 were genotyped by sequencing. Associations of variants and metabolic types with platelet reactivity (PR) were analyzed by a logistic regression model. And, a Cox proportional hazards model was utilized to analyze survival data. Confounders included gender, age, smoking status, dosage of aspirin and clopidogrel, and BMI. It was found that patients with allele A in CYP2C19*2 and *3 were susceptibility to high PR (OR, 95%CI and P values were 1.34, 1.20–1.50, <0.0001 and 1.42, 1.13–1.79, 0.0029, respectively) after taking clopidogrel. The PR increased along with the number of loss of function (LOF) allele increased and did in order of haplotype*1, *2, and *3. This research suggested that LOF alleles and risk haplotypes in CYP2C19 could significantly attenuate the response to clopidogrel, which resulted in platelet aggregation.

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Acknowledgements

We thank all the patients participating in this study. This study was supported by Starting Fund for 1000 Youth Talents (No.2013-RSQ02) and Beijing Science and Technology innovation base cultivating and developing special project (No. Z151100001615054).

Author contributions

ZZ, YT, and ZW designed this research and drafted the manuscript. ZL, WW, YF, WC, and XZ contributed to the acquisition and interpretation of the data. ZW and WL contributed to the analysis of the data.

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Authors and Affiliations

  1. State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 100037, Beijing, People’s Republic of China

    Zhifu Wang, Zhaohui Liu, Yuanyuan Fu, Wen Chen, Wenke Li & Zhou Zhou

  2. Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 100037, Beijing, People’s Republic of China

    Wenyao Wang & Yida Tang

  3. Information Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 100037, Beijing, People’s Republic of China

    Xue Zhang

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  1. Zhifu Wang
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Correspondence to Yida Tang or Zhou Zhou.

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Wang, Z., Liu, Z., Wang, W. et al. Two common mutations within CYP2C19 affected platelet aggregation in Chinese patients undergoing PCI: a one-year follow-up study. Pharmacogenomics J 19, 157–163 (2019). https://doi.org/10.1038/s41397-018-0036-2

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