PXR polymorphisms have impact on the clinical efficacy of clopidogrel in patients undergoing percutaneous coronary intervention

• Published in: Gene Vol. 653; pp. 22 - 28
• Main Authors: Wu, Yan, Yu, Hua, Tang, Hai-qin, Su, Yong, Shi, Tian-lu, Liu, Sheng, Xia, Quan, Xu, Du-juan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.05.2018
• Subjects: Clopidogrel; Major adverse cardiac event; NR1I2; Percutaneous coronary intervention; Polymorphism; PXR; ABCB1; CLP; CRV; NR1I2; Percutaneous coronary intervention; PXR; ADP; SNP; CYP450; MACE; HWE; ACEI; DAPT; HPLC; CCB; P-gp; EDTA; ARB; PCI; TEG; LD; LTA; CLPM; Clopidogrel; CHD; MAR; Polymorphism; Major adverse cardiac event
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2018.02.022

Clopidogrel is widely used in Coronary Heart Disease (CHD) patients undergoing percutaneous coronary intervention (PCI) to prevent thrombotic events. However, clopidogrel response variability (CRV) may affect the patients' clinical outcomes. The current data have shown that genetic factors play an important role in CRV. The aim of this research is to investigate the association of pregnane X receptor (PXR, also called NR1I2) genetic polymorphisms with the clinical efficacy of clopidogrel in patients undergoing PCI. A total of 384 patients undergoing PCI were recruited and treated with dual antiplatelet therapy (DAPT) for 12 months. The plasma concentration of clopidogrel carboxylic acid metabolites (CLPM) was measured by High Performance Liquid Chromatography (HPLC). The maximum aggregation rate (MAR) of platelet were measured by PL-11 analyzer. PXR genetic polymorphisms were determined by Sequenom MassArray system. The clinical outcomes were observed by readmission, outpatient and calling back interview within 12 months after PCI. Among all 384 patients, a total of 153 patients were occurred with major adverse cardiovascular events (MACE), 29 patients were occurred with bleeding events, the other patients had a favorable prognosis. The polymprphisms of PXR rs3814057A > C [OR(95%CI): 0.71(0.527–0.957), P = 0.024], rs3814058T > C [OR (95%CI): 1.395(1.034–1.883), P = 0.029] and rs6785049 A > G [OR(95%CI): 0.724 (0.535–0.979), P = 0.036] were significantly associated with MACE. The haplotype h1 (GCC) was associated with a higher risk of MACE [OR (95%CI): 1.385 (1.028–1.866), P = 0.031]. Whereas, the haplotype h2 (AAT) was associated with a lower risk of MACE [OR (95%CI): 0.711(0.525–0.962), P = 0.027]. The genotypes and haplotypes of PXR rs3814057, rs3814058 and rs6785049 have impact on the MACE in clopidogrel treated patients after PCI. •Calculated the reference range of MAR and CLPM concentration in study patients.•The 10 SNPs of PXR were firstly studied in clopidogrel treated patients.•PXR genotypes and haplotypes were firstly proved to be associated with MACE.