Clinical Study Of Clopidogrel Resistance And CYP2C19 Gene Polymorphism In Patients With Diabetic PCI

Objective:To investigate the occurrence of Clopidogrel resistance(CR)in patients with diabetes after percutaneous Coronart intervention(PCI).Then we analyzed the CYP2C19genotype of patients with clopidogrel resistance,and compared the distribution difference of CYP2C19 genotype between the diabetic CR group and the non diabetic CR group.Methods:A total of 325 patients who received PCI treatment from July 2015 to July 2016in Department of Cardiology,Laoshan Hospital Affiliated to Qingdao University were randomly selected.These patients need to meet one of the following requirements before collecting blood samples:(1)continuous taking clopidogrel for 75mg/d,more than 4days;(2)after taking clopidogrel 300mg,continue to take the regular dose of 75mg/d.They were divided into diabetes group(n=98)and non diabetic group(n=227),according to whether they had type 2 diabetes.The adenosine Diphosphat Inhibition Rate(ADP-IR%)was measured by Thrombelastography(TEG).When ADP-IR%was less than 30%,it was considered to be clopidogrel resistance.And then,the incidence of CR in two groups was obtained.Patients with clopidogrel resistant were divided into two groups according to whether they had diabetes or not.A total of 64 blood samples from all ADP-IR%<30%patients were collected again.CYP2C19 gene was detected by pyrosequencing,and finally,the CYP2C19 gene distribution was compared between the two groups.Results:1.The two groups in age,gender,smoking and hypertension baseline level was not statistically significant difference(P>0.05),while the differences in fasting blood glucose and glycosylated hemoglobin levels are statistically significant(P<0.05).2.The rate of platelet inhibition induced by ADP in diabetic and non diabetic patients was(54.88�24.38)%and(63.25�20.21)%.In 64 case(19.69%)of CR patients,there were26 case of patients with diabetes(26/98,26.53%)and 38 case of patients with no diabetes(38/227,16.74%).The proportion of patients with ADP-IR%<30%in diabetes group was significantly higher than that in non diabetic group,And the difference between the two groups was statistically significant(?~2=4.15,P<0.05).The single factor regression analysis also showed that diabetes was associated with CR(R=0.113,P<0.05).3.Logistic regression analysis showed that fasting blood glucose and glycosylated hemoglobin levels were not related to the occurrence of CR in diabetic patients.4.The CYP2C19 genotypes were detected in 64 patients in this study,including extensive metabolizers(CYP2C19*1/*1)of 30 cases(46.87%),12 cases of patients with diabetes(12/26,46.15%),18 cases of patients with non diabetic(18/38,47.37%);intermediate metabolizers(CYP2C19*1/*2,CYP2C19*1/*3)of 25 cases(39.06%),10 cases of patients with diabetes(10/26,38.46%),15 cases of patients with non diabetic(15/38,39.47%);slow metabolism(CYP2C19*2/*2,CYP2C19*2/*3,CYP2C19*3/*3)of 9 cases(14.07%),4 cases of patients with diabetes(4/26,15.39%),5 cases of patients with non diabetic(5/38,13.61%).There was no significant difference in the distribution of CYP2C19 genotype between the diabetic group and the non diabetic group(P>0.05).Conclusions:The ADP-IR%in the diabetic group and the non diabetic group were(54.88�24.38)%and(63.25�20.21)%respectively.The overall incidence of CR was19.69%,and the incidence of diabetes in the diabetic group was 26.53%.Diabetes is associated with CR,but there is no correlation between fasting blood glucose and glycosylated hemoglobin levels in diabetic people with CR.There was no significant difference in the distribution of CYP2C19*1/*1,CYP2C19*1/*2,CYP2C19*1/*3,CYP2C19*2/*2,CYP2C19*2/*3 and CYP2C19*3/*3 genotypes between the diabetic group and the non-diabetic group in the clopidogrel resistance(P>0.05).