Association of FMO3 rs1736557 polymorphism with clopidogrel response in Chinese patients with coronary artery disease
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PHARMACOGENETICS
Association of FMO3 rs1736557 polymorphism with clopidogrel response in Chinese patients with coronary artery disease Kong-Xiang Zhu 1,2 & Pei-Yuan Song 1,2 & He-Li 1,2 & Mu-Peng Li 1,2 & Yin-xiao Du 1,2 & Qi-lin Ma 3 & Li-Ming Peng 1,2,3 & Xiao-Ping Chen 1,2,4 Received: 8 June 2020 / Accepted: 14 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Dual antiplatelet therapy with aspirin and clopidogrel is commonly used for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention to prevent stent thrombosis and ischemic events. However, some patients show high on-treatment platelet reactivity (HTPR) during clopidogrel therapy. Genetic factors such as loss-of-function variants of CYP2C19 are validated to increase the risk of HTPR. Flavin-containing monooxygenase 3 (FMO3) is reported to be associated with potency of platelet responsiveness and thrombosis. This study aimed to explore the association between FMO3 rs1736557 polymorphism and clopidogrel response. Methods Five hundred twenty-two Chinese CAD patients treated with dual antiplatelet therapy were recruited from Xiangya Hospital. After oral administration of 300 mg loading dose (LD) clopidogrel for 12–24 h or 75 mg daily maintenance dose (MD) clopidogrel for at least 5 days, the platelet reaction index (PRI) was determined by vasodilator-stimulated phosphoproteinphosphorylation assay. FMO3 rs1736557, CYP2C19*2, and CYP2C19*3 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Mean PRI value was significantly higher in CYP2C19 poor metabolizers (PMs) and intermediate metabolizers (IMs) than the extensive metabolizers (EMs) (p < 0.001). In addition, FMO3 rs1736557 AA homozygotes showed significantly lower PRI as compared with carriers of the major rs1736557 G allele in the entire cohort and in the MD cohort (p = 0.011, p = 0.008, respectively). The risk of HTPR was decreased significantly in carriers of the rs1736557 A allele (AA vs GG: OR = 0.316, 95% CI: 0.137–0.726, p = 0.005; AA vs GA: OR = 0.249, 95% CI: 0.104–0.597, p = 0.001; AA vs GG+GA: OR = 0.294, 95% CI: 0.129–0.669, p = 0.002), and the association was observed mainly in patients carrying the CYP2C19 LOF allele and in those administered with MD. Conclusion The FMO3 rs1736557 AA genotype was related to an increased the antiplatelet potency of clopidogrel in Chinese CAD patients. Additional studies are required to verify this finding. Keywords Coronary artery disease . FMO3 . CYP2C19 . Platelet reaction index . High on-treatment platelet reactivity
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-020-03024-6) contains supplementary material, which is available to authorized users. * Li-Ming Peng [email protected] * Xiao-Ping Chen [email protected] 1
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China
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Institut
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