| Objective:1. To observe the efficiency of ticagrelor in the patients with acute coronary syndrome (ACS) undergoing percutaneous conronary intervention (PCI) by thrombelastography, major adverse cardiovansculor events and the risk factors.2. To investigate the impact of P2Y12 and ABCB1 gene polymorphism on the antiplatelet activity of ticagrelor, and explore the genetic causes of individual differences.Methods:1. Clinical data of 292 ACS patients who were treated with aspirin combined with ticagrelor and monitored by thrombelastography (TEG) in our department from March 2014 to May 2015 were collected in this study. They were all followed up for 12 months after charge for the recurrence of major adverse cardiovascular events (MACE) and side effects. All the patients were divided into 3 groups according to the inhibition rate in adenosine diphosphate (ADP) pathway of TEG results, Group A (ADP%?50%, N=42), Group B(ADP% 50%?75%, N=52), Group C(ADP%>75%, N=198). The efficiency of ticagrelor was compared among the 3 groups, and the risk factors for recurrence of MACE were analyzed.2. There were 224 DNA samples of above patients, Group A (N=29), Group B (N=34), Group C (N=161), and DNA was extracted. P2Y12 gene candidate single nucleotide polymorphisms (SNPs) and ABCB1 gene SNP genotypes were analysed by direct sequencing method and the mass spectrometry (MassARRAY). Linkage disequilibrium and the haplotype of gene P2Y12 were analysed by Haploview 4.2 software. The difference of inhibition rate in ADP pathway among diffenent genotypes were analysed.Results:1. Gender ratio among three groups of patients was statistically significant (P=0.001), the female rate in Group A and Group B were higher than in Group C (38.10%? 36.54% vs 17.17%, P=0.002). There were no difference among three groups on other clinical characterristics (P>0.05). The Kaplan-Meier survival analysis showed the incidence of MACE was 6.17%,21.46%,13.59% respectively in the three groups (P=0.146), the incidence of angina pectoris recurrence were 48.42%,46.73%,44.71% respectively (P=0.638). Cox regression analysis suggested that the risk factors for MACE were eGFR (B-0.020, OR 0.980,95%CI 0.962-0.999, P=0.043). There was no fatal bleeding events, and the risk factor of inactive bleeding events was female (B 0.886, OR 2.426,95%CI 1.215-4.845, P=0.012). There were 18 (6.16%) patients suffering from dyspnea, and 7 cases of them discontinued ticagrelor using due to intolerance of dyspnea.2. In the number of 20 SNPs of P2Y12 gene, rs16863348 and rs9856118 have no gene mutation. Except for rs 1491974 (P=0.024), other SNPs conform to Hardy-Weinbery test (P>0.05). There were no difference of inhibition rate in ADP pathway among diffenent genotypes (P>0.05); the P2Y12 rs6787801 genotype have difference between Group A and Group C (P=0.048), compared with AG genotype, AA genotype have higher rate in Group A than in Group C (50% vs 23.28%, P=0.013). P2Y12 rs6787801 gene mutation has higher inhibition rate in ADP pathway (OR 0.348, 95%CI 0.125-0.966, P=0.043, AG/AA). P2Y12 candidate SNPs was divided into one haplotype, Block 1(rs6793061?rs 1463725), there were no correlation between haplotypes and the inhibition rate in ADP pathway (P>0.05).Conclusion:1. There are more female patients in the hyporesponsiveness group to ticagrelor. ACS patients with lower eGFR are more likely to have recurrence of MACE, and female patients are prone to experiencing inactive bleeding events.2. Compared with AG genotype, patients with P2Y12 rs6787801 AA genotype affect the anti-platelet activity of ticagrelor.3. rs6787801 locates in the introns of P2Y12 gene, its mutation does not affect the protein traits of P2Y12 gene encoding, but may affect the amount of protein expression, which need further proofed. |
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