The effect of Xuefu Zhuyu decoction on clopidogrel resistance and its association with the P2Y12 Gene polymorphisms and promoter DNA methylation

被引:4
作者
Yu, Qinglin [1 ]
Su, Jia [2 ]
Zhu, Keqi [1 ]
Yang, Shujun [3 ]
Zhu, Hao [4 ]
Yu, Jingbo [2 ]
机构
[1] Ningbo 1 Hosp, Dept Tradit Chinese Internal Med, Ningbo, Zhejiang, Peoples R China
[2] Ningbo 1 Hosp, Dept Gerontol, Ningbo, Zhejiang, Peoples R China
[3] Ningbo 1 Hosp, Dept Hematol, Ningbo, Zhejiang, Peoples R China
[4] Ningbo 1 Hosp, Dept Anaesthesia, Ningbo, Zhejiang, Peoples R China
关键词
Xuefu Zhuyu decoction; clopidogrel resistance; P2Y12; polymorphisms; promoter DNA methylation; PERCUTANEOUS CORONARY INTERVENTION; TREATMENT PLATELET REACTIVITY; ANTIPLATELET THERAPY; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; BLOOD-CIRCULATION; PRASUGREL; DETERMINANTS; METAANALYSIS; EXPRESSION;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Some patients experience lesser degrees of platelet inhibition, which is known as clopidogrel resistance (CR). The goal of our study was to investigate the effects of Xuefu Zhuyu decoction on CR in coronary artery disease patients and whether P2Y12 polymorphisms and its methylation were related to drug response or not. 49 patients diagnosed with CR were randomly divided into control and treatment groups. Platelet functions were measured using Verify-Now P2Y12 assay. By restriction fragment length polymorphism-polymerase chain reaction, the single-nucleotide polymorphisms of rs2046934 and rs6785930 were genotyped. Using bisulphite pyrosequencing assay, we investigated the association of the P2Y12 gene DNA methylation levels and the effects of Xuefu Zhuyu decoction on CR. The results showed that the decoction improved CR (P= 0.005), and the patients with the TT genotype in rs2046934 received substantial benefits from Xuefu Zhuyu Decoction, in both P2Y12 reaction units (PRU) and inhibition percentage (P-PRU= 0.016; P-inhibition percentage = 0.028). And patients with lower methylation levels of CpG1 were more likely to be TT carriers in rs2046934 (CpG1(TT) Vs. CpG1(TC+CC)(%): 39.47 +/- 6.20 vs.45.70 +/- 8.47, P=0.044). In conclusion, our study indicated that Xuefu Zhuyu decoction might be useful for overcoming CR and the polymorphism of rs2046934 might influence the drug effect.
引用
收藏
页码:2565 / 2572
页数:8
相关论文
共 36 条
  • [31] Influence of Diabetes Mellitus and Cigarette Smoking on Variability of the Clopidogrel-Induced Antiplatelet Effect and Efficacy of Active Management of the Target P2Y12 Reaction Unit Range in Patients Undergoing Neurointerventional Procedures
    Nakagawa, Ichiro
    Park, Hun Soo
    Yokoyama, Shohei
    Wada, Takeshi
    Hironaka, Yasuo
    Motoyama, Yasushi
    Takayama, Katsutoshi
    Kichikawa, Kimihiko
    Nakase, Hiroyuki
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, 2016, 25 (01) : 163 - 171
  • [32] Associations between P2RY12 gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCI in patients with acute coronary syndrome
    Li, Miaonan
    Wang, Hongju
    Xuan, Ling
    Shi, Xiaojun
    Zhou, Tong
    Zhang, Ningru
    Huang, Yuli
    MEDICINE, 2017, 96 (14)
  • [33] Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial
    Pereira, Naveen L.
    Farkouh, Michael E.
    So, Derek
    Lennon, Ryan
    Geller, Nancy
    Mathew, Verghese
    Bell, Malcolm
    Bae, Jang-Ho
    Jeong, Myung Ho
    Chavez, Ivan
    Gordon, Paul
    Abbott, J. Dawn
    Cagin, Charles
    Baudhuin, Linnea
    Fu, Yi-Ping
    Goodman, Shaun G.
    Hasan, Ahmed
    Iturriaga, Erin
    Lerman, Amir
    Sidhu, Mandeep
    Tanguay, Jean-Francois
    Wang, Liewei
    Weinshilboum, Richard
    Welsh, Robert
    Rosenberg, Yves
    Bailey, Kent
    Rihal, Charanjit
    JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 324 (08): : 761 - 771
  • [34] Prasugrel achieves greater and faster P2Y12 receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease
    Wallentin, Lars
    Varenhorst, Christoph
    James, Stefan
    Erlinge, David
    Braun, Oscar Oe
    Jakubowski, Joseph A.
    Sugidachi, Atsuhiro
    Winters, Kenneth J.
    Siegbahn, Agneta
    EUROPEAN HEART JOURNAL, 2008, 29 (01) : 21 - 30
  • [35] Association of polymorphisms of platelet receptors GPIa (807C > T), GPVI (13254T > C), and P2Y12 (34C > T and H1/H2 haplotype) with increased risk of periprocedural bleeding in patients undergoing coronary angiography/percutaneous coronary intervention
    Sionova, Magdalena
    Blasko, Peter
    Jirous, Stepan
    Vindis, David
    Rokyta, Richard
    Motovska, Zuzana
    POSTEPY W KARDIOLOGII INTERWENCYJNEJ, 2017, 13 (03): : 202 - 209
  • [36] 4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y12 Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel
    Caroff, Eva
    Hubler, Francis
    Meyer, Emmanuel
    Renneberg, Dorte
    Gnerre, Carmela
    Treiber, Alexander
    Rey, Markus
    Hess, Patrick
    Steiner, Beat
    Hilpert, Kurt
    Riederer, Markus A.
    JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (23) : 9133 - 9153