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Background . Clopidogrel inhibits the ADP receptor  P2Y12  to keep down the platelet aggregation. The goal of our study is to investigate the contribution of  P2Y12  promoter DNA methylation to the risk of clopidogrel resistance (CR).  Methods . The platelet functions were measured by the VerifyNow  P2Y12  assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides on  P2Y12  promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association among  P2Y12  DNA methylation, various biochemical characteristics, and CR.  Result . Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1,  P  = 0.009; CpG2,  P  = 0.022) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients ( P  = 0.026) and in subgroup of Albumin < 35 ( P  = 0.002). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR.  Conclusions . The evidence from our study indicates that  P2Y12  methylation may bring new hints to elaborate the pathogenesis of CR.

Association ofP2Y12Gene Promoter DNA Methylation with the Risk of Clopidogrel Resistance in Coronary Artery Disease Patients