Abstract
Polymorphisms of CYP2C19 are associated with platelet response to clopidogrel. This study was conducted to evaluate the contribution of the previously identified polymorphisms to the response of clopidogrel in a cohort of Chinese Han patients. A total of 222 acute coronary syndrome patients undergoing percutaneous coronary intervention treated with clopidogrel were enrolled from September 2012 to June 2013. Residual platelet aggregations for all patients were measured by the VerifyNow P2Y12 system. Sixteen single-nucleotide polymorphisms among nine genes were genotyped including CYP2C19, ABCB1 and PON1. In this study, CYP2C19*2 and CYP2C19*17 were strongly associated with higher platelet aggregation and lower platelet aggregation to clopidogrel treatment, respectively (P<0.001). Patients with CYP2C19*2 allele had a higher risk of high on-treatment platelet reactivity than non carriers (adjusted OR, 5.434; 95% CI, 1.918–15.399, P=0.01). The coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and the coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were also associated with poor response to clopidogrel. No significant relation of CYP2C19*3 and other polymorphisms to the platelet aggregation was found. In conclusion, CYP2C19*2, CYP2C19*17 coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were identified to be associated with response to clopidogrel treatment in Chinese Han patients.
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Acknowledgements
Authors thank all the subjects included in this study and the staff in Department of Cardiology of EAST Hospital and Fudan Center for Genetic Epidemiology for their support. This study was supported by a grant from the Shanghai Health Bureau (20124282). This study was partially supported by research funds from the Shanghai Municipal Health Bureau (20124035), from School of Public Health of Fudan University (to JX) and the State Key Laboratory of Genetic Engineering of Fudan University (to SLZ).
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[Liu X., Luo Y., Lai Y., Yao Y., Li J., Wang Y., Zheng S. L., Xu J. and Liu X. 2016 Effect of genetic and coexisting polymorphisms on platelet response to clopidogrel in Chinese Han patients with acute coronary syndrome. J. Genet. 95, xx–xx]
Xu Liu and Yu Luo contributed equally to this work
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LIU, X., LUO, Y., LAI, Y. et al. Effect of genetic and coexisting polymorphisms on platelet response to clopidogrel in Chinese Han patients with acute coronary syndrome. J Genet 95, 231–237 (2016). https://doi.org/10.1007/s12041-016-0618-1
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DOI: https://doi.org/10.1007/s12041-016-0618-1