Literature DB >> 23506580

Effects of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and clinical outcome in patients with acute coronary syndromes undergoing stent-based coronary intervention.

Xiao-Fang Tang1, Jia-Hui Zhang, Jing Wang, Ya-Ling Han, Bo Xu, Shu-Bin Qiao, Yong-Jian Wu, Jue Chen, Yuan Wu, Ji-Lin Chen, Run-Lin Gao, Yue-Jin Yang, Jin-Qing Yuan.   

Abstract

BACKGROUND: The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients.
METHODS: In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.
RESULTS: Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74 ± 32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%).
CONCLUSION: Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.

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Year:  2013        PMID: 23506580

Source DB:  PubMed          Journal:  Chin Med J (Engl)        ISSN: 0366-6999            Impact factor:   2.628


  11 in total

1.  Effect of genetic and coexisting polymorphisms on platelet response to clopidogrel in Chinese Han patients with acute coronary syndrome.

Authors:  Xu Liu; Yu Luo; Yan Lai; Yian Yao; Jimin Li; Yunkai Wang; S Lilly Zheng; Jianfeng Xu; Xuebo Liu
Journal:  J Genet       Date:  2016-06       Impact factor: 1.166

2.  Genetic polymorphisms of high platelet reactivity in Chinese patients with coronary heart disease under clopidogrel therapy.

Authors:  Xiao Zou; Xin-Li Deng; Yin-Meng Wang; Jian-Hua Li; Lin Liu; Xin Huang; Lu Liu; Jian Cao; Li Fan
Journal:  Int J Clin Pharm       Date:  2020-04-06

Review 3.  Clinical pharmacokinetics and pharmacodynamics of clopidogrel.

Authors:  Xi-Ling Jiang; Snehal Samant; Lawrence J Lesko; Stephan Schmidt
Journal:  Clin Pharmacokinet       Date:  2015-02       Impact factor: 6.447

4.  Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population.

Authors:  R Priyadharsini; G Umamaheswaran; T A R Raja; A S Arun Kumar; K Subraja; S A Dkhar; S Satheesh; C Adithan; D G Shewade
Journal:  J Community Genet       Date:  2017-03-02

5.  Dynamic changes and associated factors of clopidogrel resistance in patients after cerebral infarction.

Authors:  Bo Rong Zhou; Hong Ting Shi; Rong Wang; Min Zhang; Hai Tao Guan; Zi Fan Liu; Yan Hua Deng
Journal:  J Neurol       Date:  2013-10-18       Impact factor: 4.849

6.  Effects of CYP2C19 and P2Y12 Gene Polymorphisms on Clinical Results of Patients Using Clopidogrel after Acute Ischemic Cerebrovascular Disease.

Authors:  H M Sen; F Silan; C Silan; Y Degirmenci; H I Ozisik Kamaran
Journal:  Balkan J Med Genet       Date:  2015-04-10       Impact factor: 0.519

7.  Associations between P2RY12 gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCI in patients with acute coronary syndrome.

Authors:  Miaonan Li; Hongju Wang; Ling Xuan; Xiaojun Shi; Tong Zhou; Ningru Zhang; Yuli Huang
Journal:  Medicine (Baltimore)       Date:  2017-04       Impact factor: 1.889

Review 8.  The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics.

Authors:  Arwa M Amin; Lim Sheau Chin; Dzul Azri Mohamed Noor; Muhamad Ali Sk Abdul Kader; Yuen Kah Hay; Baharudin Ibrahim
Journal:  Cardiol Res Pract       Date:  2017-03-21       Impact factor: 1.866

Review 9.  Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine.

Authors:  Sherry-Ann Brown; Naveen Pereira
Journal:  J Pers Med       Date:  2018-01-30

10.  Influence of cytochrome P450 polymorphisms on the antiplatelet effects of prasugrel in patients with non-cardioembolic stroke previously treated with clopidogrel.

Authors:  Takanari Kitazono; Yasuo Ikeda; Masakatsu Nishikawa; Satoshi Yoshiba; Kenji Abe; Akira Ogawa
Journal:  J Thromb Thrombolysis       Date:  2018-11       Impact factor: 2.300

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