Influences Of P2Y12 (C34T,G52T,iT744C) Polymorphisms On Clopidogrel Resistance In Patients With Coronary Heart Disease

Objective: To investigate the contribution of P2Y12 genetic(C34T,G52T, iT744C)polymorphisms in Chinese health volunteers and patients with CHD,and to explore the the association between P2Y12 genetic polymor- phisms and labortary clopidogrel resistance in patients with CHD.Methods: 548 CHD patients (369 male and 179 female ,mean age 66.77±11.33 years),including 103 patients underwent percutaneous coronary interven- tion (PCI) ,and 222 healthy volunteers (131 male and 91 female,mean age 59.45±10.45 years) were enrolled to identify P2Y12 C34T,G52T, iT744C genotypes by polymerase chain reaction-restriction fragment length polymorphism assay. 260 patients with different genotypes received orally clopidogrel as a single-dose therapy (75mg day-1 p.o.) for 10 days. Inhibition of ADP-induced platelet aggregation percentage was determined before and after clopidogrel treatment.Finally,to analyze the association of didderent genotypes of P2Y12 with ADP-induced platelet aggregation, clopidogrel resistance, cardiovas- cular events in 103 PCI patients.Results:1.The three polymorphisms were in Hardy-Weinberg equilibrium. Between the CHD patients and the natural controls ,there was no significant difference in genotype frequency of C34T and G52T (P>0.05),while there was signifi- cant difference in genotype frequency of iT744C (P<0.05).2.The mean lowing rate of inhibition of platelet aggregation is 13.64±11.34% and clopidogrel resistance rate is 35.77%(93/260)in 260 patients receiving orally clopidogrel.Regarding C34T, there was a smaller reduction in the inhibition of platelet aggregation and a smaller increase in the clopidogrel resistance for the CC genotype than for the other genotypes (P<0.01). Regarding G52T, there was no difference of inhibition of platelet aggregation and the Clopidogrel resistance rate between differ- ent genetypes. Regarding iT744C, there was a smaller reduction in the inhibition of platelet aggregation and a smaller increase in the clopido- grel resistance for the CC genotype than for the TT+TC genotypes (P<0.05).3. Because of CPY2C19*2 genetic mutation influencing clopidogrel resista- nce, we selected 135 CPY2C19*2 wildtype(GG) CHD patients.In the same way, the mean lowing rate of inhibition of platelet aggregation is 15.88±11.67% and clopidogrel resistance rate is 26.67%(36/135). Regarding C34T, there was a smaller reduction in the inhibition of platelet aggregation and a smaller increase in the clopidogrel resistance for the CC genotype than for the other genotypes (P<0.05). Regarding G52T and iT744C, there was no difference of inhibition of platelet aggregation and the clopido- grel resistance rate between different genetypes.4.103 PCI patients had been given a follow-up visit and the second cardiovascular events frequency is 29.13%(30/103).Our study showed no significant difference between cardiovascular events frequency and P2Y12(C34T,G52T,iT744C) polymorphisms (P>0.05).Conclusion: These data suggest that the P2Y12 allele 34C>T polymorphism is significantly associated with clopidogrel resistance in Chinese patients with CHD, independent of CPY2C19*2 polymorphisms effect. G52T polymorphism is no associated with clopidogrel resistance. Regarding iT744C,CC genotype maybe associate with clopidogrel resistance,but CPY2C19*2 polymorphisms may play a greater role in it.