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.
Highlights
At sites of vascular injury due to atherosclerotic plaque rupture or erosion, platelets mediate haemostasis and pathologic thrombosis[1]
Patients with poor clopidogrel response were more likely to be female and have hypertension and lower albumin levels. These data indicated that female sex, hypertension and lower albumin levels might increase the risk of clopidogrel resistance
With the application of the Verify- P2Y12 assay for platelet function tests in clinical practice and the use of polymerase chain reaction-high performance capillary electrophoresis (PCR-HPCE) for sequencing, we found that if patients had no hypoproteinaemia or had hypertension, the single-nucleotide polymorphisms (SNPs) in rs1045642 was associated with clopidogrel resistance (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)
Summary
At sites of vascular injury due to atherosclerotic plaque rupture or erosion, platelets mediate haemostasis and pathologic thrombosis[1]. A large number of patients continue to suffer recurrent ischaemic events[5], and this clinical phenomenon has been correlated with lesser degrees of platelet inhibition[6]. This failure of the antiplatelet drug to inhibit its target of action is called clopidogrel non-responsiveness or clopidogrel resistance[7]. Both prasugrel and ticagrelor, which are novel and stronger antiplatelet agents, were shown to exert more consistent, rapid and effective P2Y12 receptor inhibition in patients with acute coronary syndrome (ACS)[8]. Clopidogrel remains to be one of the most extensively prescribed antiplatelet drugs in CAD patients, and research focused on the individual susceptibility to clopidogrel is of vital significance
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