GENETIC CHARACTERISTICS ASSOCIATED WITH CLOPIDOGREL RESISTANCE

Đình Cẩm Trương, Anh Hoàng Tạ, Văn Công Thắng Trần, Bắc An Lương, Gia Hoàng Linh Lê, Đức Minh Đỗ

Main Article Content

Abstract

Background: Clopidogrel, an antiplatelet drug, is a cornerstone treatment in coronary artery disease. However, the efficacy of inhibiting platelet aggregation of clopidogrel depends on many aspects, especially the patients’ genetic factor. Objectives: To investigate the associations of single nucleotide polymorphisms on CYP2C19, PON1 gene including rs4244285, rs4986893, and rs662 with clopidogrel resistance. Methods: 198 patients diagnosed with coronary artery disease and indicated clopidogrel were recruited in this study. Genomic DNA was extracted from patients’ peripheral blood samples and the genotypes of rs4244285, rs4986893, and rs662 were identified by PCR method. Platelet aggregation was measured by optical aggregometry with ADP. Results: There were 121 patients with clopidogrel resistance. The 3 polymorphisms rs4244285, rs4986893, rs662 showed no statistical association with clopidogrel resistance. However, patients with G/A/T haplotype had 4 times higher risk of clopidogrel resistance compared with patients not carrying this haplotype. Conclusions: The study has primarily described the association of rs4244285, rs4986893, and rs662 with clopidogrel resistance in Vietnamese patients.

Article Details

References

1. Patti G, Micieli G, Cimminiello C, Bolognese L. The Role of Clopidogrel in 2020: A Reappraisal. Cardiovasc Ther. 2020;2020:8703627.
2. Shuldiner AR, O’Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009 Aug 26; 302(8):849–57.
3. Cuisset T, Morange PE, Quilici J, Bonnet JL, Gachet C, Alessi MC. Paraoxonase-1 and clopidogrel efficacy. Nat Med. 2011 Sep;17(9):1039–1039.
4. Vũ Diễm My, Lương Bắc An, Bùi Hữu Hoàng, Đỗ Thị Thanh Thủy. Xây dựng quy trình xác định tính đa hình gen cytochrome P450 2C19 (CYP2C19) bằng phương pháp Multiplex Real-time PCR. Tạp Chí Học Thành Phố Hồ Chí Minh. 2016; 20(1):115–21.
5. Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinforma Oxf Engl. 2006 Aug 1;22(15):1928–9.
6. Lewis JP, Backman JD, Reny JL, Bergmeijer TO, Mitchell BD, Ritchie MD, et al. Pharmacogenomic polygenic response score predicts ischaemic events and cardiovascular mortality in clopidogrel-treated patients. Eur Heart J-Cardiovasc Pharmacother. 2020 Jul;6(4):203–10.
7. Li X, Wang Z, Wang Q, Xu Q, Lv Q. Clopidogrel-associated genetic variants on inhibition of platelet activity and clinical outcome for acute coronary syndrome patients. Basic Clin Pharmacol Toxicol. 2019;124(1):84–93.
8. Su Q, Li J, Tang Z, Yang S, Xing G, Liu T, et al. Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China. Med Sci Monit Int Med J Exp Clin Res. 2019 Sep 23;25:7138–48.