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

被引:6
作者
Wang, Zhifu [1 ,2 ]
Liu, Zhaohui [1 ,2 ]
Wang, Wenyao [2 ,3 ]
Fu, Yuanyuan [1 ,2 ]
Chen, Wen [1 ,2 ]
Li, Wenke [1 ,2 ]
Zhang, Xue [2 ,4 ]
Tang, Yida [2 ,3 ]
Zhou, Zhou [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp,State Key Lab Cardiovasc Dis, Diagnost Lab Serv,Beijing Key Lab Mol Diagnost Ca, Beijing 100037, Peoples R China
[2] Peking Union Med Coll, Beijing 100037, Peoples R China
[3] Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis,Dept Cardiol, Beijing 100037, Peoples R China
[4] Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Informat Ctr, Beijing 100037, Peoples R China
关键词
PERCUTANEOUS CORONARY INTERVENTION; DUAL ANTIPLATELET THERAPY; PROTON PUMP INHIBITORS; GENETIC POLYMORPHISMS; CLINICAL-OUTCOMES; CLOPIDOGREL; GENOTYPE; IMPACT; RESPONSIVENESS; METABOLISM;
D O I
10.1038/s41397-018-0036-2
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:157 / 163
页数:7
相关论文
共 26 条
  • [1] Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis
    Bauer, Tim
    Bouman, Heleen J.
    van Werkum, Jochem W.
    Ford, Neville F.
    ten Berg, Jurrien M.
    Taubert, Dirk
    [J]. BMJ-BRITISH MEDICAL JOURNAL, 2011, 343
  • [2] Increased risk in patients with high platelet amregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention - Is the current antiplatelet therapy adequate?
    Bliden, Kevin P.
    DiChiara, Joseph
    Tantry, Udaya S.
    Bassi, Ashwani K.
    Chaganti, Srivasavi K.
    Gurbel, Paul A.
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (06) : 657 - 666
  • [3] Cannon Christopher P, 2013, Crit Pathw Cardiol, V12, P65, DOI 10.1097/HPC.0b013e3182846e16
  • [4] DEMORAIS SMF, 1994, MOL PHARMACOL, V46, P594
  • [5] DEMORAIS SMF, 1994, J BIOL CHEM, V269, P15419
  • [6] A RANDOMIZED COMPARISON OF CORONARY-STENT PLACEMENT AND BALLOON ANGIOPLASTY IN THE TREATMENT OF CORONARY-ARTERY DISEASE
    FISCHMAN, DL
    LEON, MB
    BAIM, DS
    SCHATZ, RA
    SAVAGE, MP
    PENN, I
    DETRE, K
    VELTRI, L
    RICCI, D
    NOBUYOSHI, M
    CLEMAN, M
    HEUSER, R
    ALMOND, D
    TEIRSTEIN, PS
    FISH, RD
    COLOMBO, A
    BRINKER, J
    MOSES, J
    SHAKNOVICH, A
    HIRSHFELD, J
    BAILEY, S
    ELLIS, S
    RAKE, R
    GOLDBERG, S
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (08) : 496 - 501
  • [7] Clopidogrel Pharmacokinetics and Pharmacodynamics Vary Widely Despite Exclusion or Control of Polymorphisms (CYP2C19, ABCB1, PON1), Noncompliance, Diet, Smoking, Co-Medications (Including Proton Pump Inhibitors), and Pre-Existent Variability in Platelet Function
    Frelinger, Andrew L., III
    Bhatt, Deepak L.
    Lee, Ronald D.
    Mulford, Darcy J.
    Wu, Jingtao
    Nudurupati, Sai
    Nigam, Anu
    Lampa, Michael
    Brooks, Julie K.
    Barnard, Marc R.
    Michelson, Alan D.
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2013, 61 (08) : 872 - 879
  • [8] Geisler T, 2011, NEW ENGL J MED, V364, P481, DOI 10.1056/NEJMc1013331
  • [9] Duration of Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation A Systematic Review and Meta-Analysis of Randomized Controlled Trials
    Giustino, Gennaro
    Baber, Usman
    Sartori, Samantha
    Mehran, Roxana
    Mastoris, Ioannis
    Kini, Annapoorna S.
    Sharma, Samin K.
    Pocock, Stuart J.
    Dangas, George D.
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2015, 65 (13) : 1298 - 1310
  • [10] Adenosine diphosphate-induced platelet-fibrin clot strength: A new thrombelastographic indicator of long-term poststenting ischemic events
    Gurbel, Paul A.
    Bliden, Kevin P.
    Navickas, Irene A.
    Mahla, Elizabeth
    Dichiara, Joseph
    Suarez, Thomas A.
    Antonino, Mark J.
    Tantry, Udaya S.
    Cohen, Eli
    [J]. AMERICAN HEART JOURNAL, 2010, 160 (02) : 346 - 354