Combined influence of ABCB1 genetic polymorphism and DNA methylation on aspirin resistance in Chinese ischemic stroke patients.

Abstract

Genetic variants ofABCB1may affect intestinal absorption of aspirin (ASA). However, it is unclear whetherABCB1polymorphisms and DNA methylation are associated with ASA efficacy for ischemic stroke. Our aims is to investigate the association betweenABCB1polymorphisms and methylation status on the antiplatelet effects of ASA in Chinese Han ischemic stroke patients. This is a prospective cohort analysis of eligible stroke patients who received ASA. Patients were divided into two groups according to the thrombelastogram and platelet aggregation test: aspirin resistance (AR) and aspirin-sensitive (AS) groups. The ABCB1 genetic polymorphism and the methylation status of promoter regions were analyzed using PCR-RFLP and the combined bisulfite restriction analysis (COBRA). The number of genotype CC + TT of C3435T in the AR group was greater than that of the AS group (p = 0.007). The DNA methylation levels of ABCB1 promoter in the AS group was higher than that of the AR group (p < 0.001), and the promoter methylation levels showed significant different among the CC, CT, and TT genotypes of C3435T individuals (p = 0.006), while there was no obvious difference between different genotypes of C1236T and G2677T/A polymorphisms (p > 0.05). We also found that the methylation status of the ABCB1 promoter correlated positively with arachidonic acid inhibition (AA%) (R = 0.781, p < 0.001).TheABCB1polymorphism and methylation status was associated with the reduced efficacy of ASA treatment in ischemic stroke. Genetic polymorphism and DNA methylation ofABCB1should be concerned when prescribing ASA.