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Cytochrome P450 2C19 polymorphism is associated with poor clinical outcomes in coronary artery disease patients treated with clopidogrel

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Abstract

Patients with lesser degrees of platelet inhibition in response to clopidogrel appear to be at increased risk for recurrent ischemic events. Cytochrome P450 (CYP) polymorphisms have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Published data on the association between CYP2C19*2 polymorphism and atherothrombotic events are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of eight prospective cohort studies including 2,345 patients carrying CYP2C19*2 variant allele and 5,935 cases with the wild-type genotype were included in this meta-analysis. Overall, borderline statistically significantly elevated risk of adverse clinical events was associated with genotyping 681G>A polymorphism (for AA + GA vs. GG: OR, 1.46; 95% CI, 1.01 to 2.13; P = 0.05). The summary odds ratio showed a significant association between the CYP2C19*2 polymorphism and an increased risk of cardiac mortality in the follow-up period (OR, 2.07; 95% CI, 1.22 to 3.52; P = 0.007). When studies evaluating myocadial infarction, stent thrombosis, and ischemic stroke, the presence of the variant allele was associated with significantly increased risks of recurrent atherothrombotic events. In summary, this meta-analysis indicated that CYP2C19*2 carrier status is significantly associated with an increased risk of adverse cardiovascular events.

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Acknowledgments

We gratefully acknowledge Dr. Ying Shan for her editorial suggestions for the article. This study was supported in part by the 11th Five-year National Science Project on Chronic Heart Failure in China (2006BAI01A04).

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The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Cardiology, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, 200040, Shanghai, China

    Bo Jin, Huan-Chun Ni, Wei Shen, Jian Li, Hai-Ming Shi & Yong Li

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  1. Bo Jin
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  2. Huan-Chun Ni
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  3. Wei Shen
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  4. Jian Li
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  5. Hai-Ming Shi
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  6. Yong Li
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Correspondence to Yong Li.

Additional information

Bo Jin and Huan-Chun Ni contributed equally to this study and should be considered as co-first authors.

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Jin, B., Ni, HC., Shen, W. et al. Cytochrome P450 2C19 polymorphism is associated with poor clinical outcomes in coronary artery disease patients treated with clopidogrel. Mol Biol Rep 38, 1697–1702 (2011). https://doi.org/10.1007/s11033-010-0282-0

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  • DOI: https://doi.org/10.1007/s11033-010-0282-0

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