The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population

Abstract

The goal of our study was to investigate the contribution of ABCB1 expression to the risk of clopidogrel resistance (CR). Platelets functions were measured using the Verify-Now P2Y12 assay. Applying Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP), the single-nucleotide polymorphisms (SNPs) was tested. Using bisulphite pyrosequencing assay, we investigated the association of the ABCB1 DNA methylation levels and CR. It was shown that female, hypertension, and lower albumin levels increased the risk of CR (P<0.05). If patients did not have hypoproteinaemia or had hypertension, the SNP in rs1045642 was associated with CR (CC vs. TT: albumin ≥35, P = 0.042; hypertension, P = 0.045; C vs. T: albumin ≥35, P = 0.033; hypertension, P = 0.040). Additionally, the platelet inhibition of the CT+TT genotype in rs1128503 was larger than that of the CC genotype (P = 0.021). Multivariate logistic regression analysis showed that male, higher albumin and hsCRP decreased the risk of CR, and the stent size maybe positively correlated with CR. The SNP in rs1045642 was related to all-cause mortality (P = 0.024). We did not find any relationship between the methylation levels of the ABCB1 promoter and CR. In conclusions, our study indicated that ABCB1 polymorphisms might be useful in further evaluating the pathogenesis of CR.

Association of PON1 gene promoter DNA methylation with the risk of Clopidogrel resistance in patients with coronary artery disease

“…The phenomenon of clopidogrel resistance was influenced by many kinds of extrinsic factors (environment, comorbidities, drug interactions, and so on) and intrinsic factors that may contribute to CR . For instance, our former study indicated that the male gender, higher albumin in males, and hyperlipidaemia decreased the CR incidence . Another study found that chronic kidney disease (CKD) appeared to be related to a poor clopidogrel response and a higher risk of stent thrombosis in PCI patients with diabetes .…”

“…For instance, ABCA1 DNA methylation was a predictive biomarker for the CAD development and was independent of plasma lipid concentration . Since 2014, several studies have explored the influence of DNA methylation in ABCB1 , P2Y12 , and cytochrome P450 enzymes on CR. This time, we chose PON1 as the target gene and found some significant results.…”

“…20 For instance, our former study indicated that the male gender, higher albumin in males, and hyperlipidaemia decreased the CR incidence. 21 Another study found that chronic kidney disease (CKD) appeared to be related to a poor clopidogrel response and a higher risk of stent thrombosis in PCI patients with diabetes. 22 In this study, after logistic regression analysis with extrinsic and intrinsic variables in the total population and the subgroup with dyslipidemia, we discovered that the quantity of stent was correlated with CR, which was similar to the findings in our former research.…”

A Multiplex Pharmacogenetics Assay using the MinION Nanopore Sequencing Device

“…Pharmacogenomics Implementation Consortium (CPIC) guidelines [13], as well as covering new 26 variants reported in recent publications [3][4][5][6]15] (Table 1). Use of a polymerase chain reaction (PCR) 27…”

“…Both CYP2C19 and CYP2C9 are 5 polymorphic genes with more than 30 known alleles [1]. Moreover, recent publications suggest that 6 other genes are also associated with variable drug response, including B4GALT2 [3] and ABCB1 [4,5] 7…”