The effect of Xuefu Zhuyu decoction on clopidogrel resistance and its association with the P2Y12 Gene polymorphisms and promoter DNA methylation

Some patients experience lesser degrees of platelet inhibition, which is known as clopidogrel resistance (CR). The goal of our study was to investigate the effects of Xuefu Zhuyu decoction on CR in coronary artery disease patients and whether P2Y12 polymorphisms and its methylation were related to drug response or not. 49 patients diagnosed with CR were randomly divided into control and treatment groups. Platelet functions were measured using Verify-Now P2Y12 assay. By restriction fragment length polymorphism-polymerase chain reaction, the single-nucleotide polymorphisms of rs2046934 and rs6785930 were genotyped. Using bisulphite pyrosequencing assay, we investigated the association of the P2Y12 gene DNA methylation levels and the effects of Xuefu Zhuyu decoction on CR. The results showed that the decoction improved CR (P= 0.005), and the patients with the TT genotype in rs2046934 received substantial benefits from Xuefu Zhuyu Decoction, in both P2Y12 reaction units (PRU) and inhibition percentage (P-PRU= 0.016; P-inhibition percentage = 0.028). And patients with lower methylation levels of CpG1 were more likely to be TT carriers in rs2046934 (CpG1(TT) Vs. CpG1(TC+CC)(%): 39.47 +/- 6.20 vs.45.70 +/- 8.47, P=0.044). In conclusion, our study indicated that Xuefu Zhuyu decoction might be useful for overcoming CR and the polymorphism of rs2046934 might influence the drug effect.