| Objective:There are many important factors leading to adult disability and death.Stroke is one of them,and ischemic stroke is an important subtype of stroke in China.Antiplatelet therapy can reduce the risk of recurrent ischemic stroke and transient ischemic attack by 25%,which is one of the main measures to prevent the recurrence of cardiovascular and cerebrovascular events.Over the years,based on numerous studies and practices,the effect of clobigray on platelet resistance has been significantly different in different patients.Even though some patients are given drugs according to the standard treatment,they still fail to prevent the recurrence of ischemic stroke and other vascular events in a timely manner,which is called clopidogrel resistance(CR).As a class of adenosine diphosphate receptor inhibitors,clobigray is itself a drug precursor,and does not show drug activity outside the body.In vivo,stem cell pigment P450(CYP450)system is involved in the transformation into active metabolites.The protease encoded by paraoxonase1(PON1)is also a member of the CYP450 family,and PON1 is reported to be a key enzyme in the conversion of 2-oxyclopidogrel into active metabolites.The gene polymorphism site most closely related to function is PON1 Q192 R,and according to the data,this gene polymorphism can play an important role in the activity and expression of serum.This study aimed to study the correlation between clopidogrel resistance and PON1 Q192 R polymorphisms in patients with ischemic stroke.Methods:Selection in February 2015 to December 2016 in the first hospital affiliated to China medical university hospital nerve internal medicine diagnosis and treatment of ischemic stroke or TIA patients,131 cases as the research object,to give all of the patients taking clopidogrel 75 mg/day,and treatment of 7 days before the treatment to detect changes in the rate of the platelet aggregation induced by ADP,70% or higher for CR group,< 70% of CR(NCR)group;Whole blood was collected and DNA was extracted.Genotypes of PON1 gene Q192 R single nucleotide polymorphisms were detected by pcr-rflp,primers and PCR conditions were added,and 5% samples were randomly selected for DNA sequencing verification.Patients with recurrent stroke were followed up for 6 months to analyze the correlation between clopidogrel resistance and PON1 Q192 R polymorphisms in ischemic stroke patients.Results:1.According to the platelet aggregation rate of more than 70%,the incidence of CR(24 cases)and NCR(107 cases)was 18.3%.There was no statistically significant difference in the general clinical data between the two groups(p>0.05).2.The distribution of 3 genotypes of PON1Q192 R loci between the two groups followed the law,and the distribution difference of the 3 genotypes between the two groups was statistically significant(p<0.05).3.Logistic regression analysis suggested that the polymorphism of PON1 Q192 locus was statistically significant for the occurrence of clopidogrel resistance(p<0.05),and the polymorphism of Q192 R locus was an independent risk factor for clopidogrel resistance.4.131 cases of ischemic stroke in patients with oral clopidogrel and after 6 months follow-up,34 patients with cerebral stroke recurrence rate was 25.95%,the incidence of CR group was 79.17%,the recurrence of cerebral apoplexy in the group of clopidogrel resistance and resistance to compare the difference was statistically significant(p < 0.001),the CR relapse rates were higher in the patients with cerebral apoplexy,recurrent stroke compared differences between different genotypes was statistically significant(p = 0.022),with A allele relapse rates were higher in the patients with cerebral apoplexy.Conclusion:1.PON1 Q192 R polymorphism is associated with clopidogrel resistance.2.PON1 Q192 R polymorphism may be one of the causes of recurrent stroke in ischemic stroke patients. |
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