Dergiler / The Anatolian Journal of Cardiology / 2017 / Cilt: 17 - Sayı: 4

Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome

Sayfa
303–312
DOI
—
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%).Conclusion: CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Objective: To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel.Methods: Cross-sectional study of 278 consecutive patients with ACS.
📊
Temel Bulgular & Veri:Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays.
💡
Sonuç & Katkı:Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%).Conclusion: CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables
🔬Tür:Modelleme & Sayısal Simülasyon
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Alan Parametreleri

Abstract

Objective: To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel.Methods: Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Platelet reactivity was measured with VerifyNow®.Results: Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01–16.34), age (OR 1.43; 95% CI 1.03–2.00), and body mass index (OR 4.05; 95% CI 1.21–13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%).Conclusion: CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables

🔖

Bu Makaleye Atıf Yap

GARCÍA-LAGUNAR, M. H., CONSUEGRA-SÁNCHEZ, L., ZAMORA, P. C., RUİZ-COSANO, J., ARCOS, F. S., GUADİANA, L. G. D., VİVAR, P. C., CASTİLLO-MORENO, J. A., MELGAREJO-MORENO, A. (2017). Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome. The Anatolian Journal of Cardiology, Cilt: 17 - Sayı: 4, 303–312. https://ajindex.com/articles/365836

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (9)

  1. Jin HY, Yang TH, Kim DI, Chung SR, Seo JS, Jang JS, et al. High post-clopidogrel platelet reactivity assessed by a point-of-care assay predicts long-term clinical outcomes in patients with ST- segment elevation myocardial infarction who underwent primary coronary stenting. Int J Cardiol 2013; 167: 1877-81.
  2. Park JJ, Park KW, Kang J, Jeon KH, Kang SH, Ahn HS, et al. Genetic determinants of clopidogrel responsiveness in Koreans treated with drug-eluting stents. Int J Cardiol 2013: 163: 79-86.
  3. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009; 360: 354-62.
  4. Ko YG, Suh JW, Kim BH, Lee CJ, Kim JS, Choi D, et al. Comparison of 2 point-of-care platelet function tests, VerifyNow Assay and Mul- tiple Electrode Platelet Aggregometry, for predicting early clinical outcomes in patients undergoing percutaneous coronary interven- tion. Am Heart J 2011; 161: 383-90.
  5. Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horen- stein RB, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009; 302: 849-57.
  6. Angiolillo DJ, Alfonso F. Platelet function testing and cardiovascu- lar outcomes: steps forward in identifying the best predictive mea- sure. Thromb Haemost 2007; 98: 707-9.
  7. Angiolillo DJ, Bernardo E, Sabate M, Jimenez-Quevedo P, Costa MA, Palazuelos J, et al. Impact of platelet reactivity on cardiovas- cular outcomes in patients with type 2 diabetes mellitus and coro- nary artery disease. J Am Coll Cardiol 2007; 50: 1541-7. Huber K. Genetic variability in response to clopidogrel therapy: clinical implications. Eur Heart J 2010; 31: 2974-6.
  8. Gladding P, Webster M, Zeng I, Farrell H, Stewart J, Ruygrok P, et al. The pharmacogenetics and pharmacodynamics of clopidogrel res- ponse: an analysis from the PRINC (Plavix Response in Coronary Intervention) trial. JACC Cardiovasc Interv 2008; 1: 620-7.
  9. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramírez C, Cavallari U, Trabetti E, et al. Contribution of gene sequence variations of the hepatic cytochrome P450 3A4 enzyme to variability in individual res- ponsiveness to clopidogrel. Arterioscler Thromb Vasc Biol 2006; 26: 1895-900. Harmsze AM, van Werkum JW, Ten Berg JM, Zwart B, Bouman HJ, Breet NJ, et al. CYP2C19*2 and CYP2C9*3 alleles are associated with stent thrombosis: a case-control study. Eur Heart J 2010; 31: 3046-53. Harmsze A, van Werkum JW, Bou