ABCB1 hypomethylation is associated with decreased antiplatelet effects of clopidogrel in Chinese ischemic stroke patients.

摘要: Current predictive models including the CYP2C19 polymorphism and clinical factors still explain only about 12% of variability clopidogrel responsiveness. Up until recently, precise mechanism resistance remains unclear. P-glycoprotein (P-gp) encoded by ABCB1, a transmembrane calcium-dependent efflux pump for clopidogrel, implicated role in resistance. In this present study, we investigated methylation status ABCB1 gene promoter relation to mRNA expressions antiplatelet effects clopidogrel. This study was prospective cohort analysis eligible stroke patients (n = 183, aged 18-75 years) who received (75 mg/day) at least 5 days before discharge. A final subcohort 87 with CYP2C19*1/*1 genotype were enrolled population. Patients grouped quartiles maximum platelet aggregation (MPA values (Q1, Q2, Q3 Q4, MPA(Q1) 35.4%). The 1.8 times Q1 MPA group (10.1 ± 2.4%) than Q4 (5.5 2.1%) (P < 0.001). correlated inversely (R - 0.764, P 0.001) expression 0.839, Results multivariate linear regression model demonstrated that independently associated (β(coef ficient) 4.71, 0.62 (5.3 1.4 per thousand) (8.5 2.5%o), positively ADP-induced 0.791, whole blood appears be MPA. conclusions, hypomethylation is decreased response ischemic via increased expression.