缺血性脑卒中患者CYP2C19基因多态性分布与预后的相关性研究OA

OBJECTIVE:To probe into the distribution characteristics of CYP2C19 gene polymorphisms in patients with ischemic stroke(IS)and its effects on efficacy of antiplatelet therapy,coagulation function,and clinical prognosis.METHODS:Patients undergoing CYP2C19 genotyping at Beijing Shijitan Hospital,Capital Medical University from Jun.2019 to Dec.2023 were retrospectively enrolled.Demographic data,severity and comorbidity of ischemic stroke,coagulation parameters,recurrence and rehospitalization were collected to analyze the correlation between CYP2C19 gene polymorphisms and the severity of ischemic stroke,risk of comorbidity,platelet aggregation rate,abnormal rates of coagulation indicators,and readmission due to IS recurrence.RESULTS:A total of 680 IS patients were enrolled.The minor allele frequencies of CYP2C19 2,3,and 17 were respectively 31.18％,6.76％,and 1.40％,and the distributions were in Hardy-Weinberg equilibrium(P>0.05).No significant differences were observed in the incidences of moderate to severe IS,hypertension,diabetes,and coronary heart disease among different genotypes,alleles,haplotypes,and metabolizer groups at each locus(P>0.05).The median adenosine diphosphate-induced platelet aggregation rate(ADP-PAG)in CYP2C19 2 GG genotype patients(31.60％)was significantly lower than that in GA genotype group(45.60％,P<0.01)and AA genotype group(52.80％,P<0.01);the median ADP-PAG in CYP2C19 3 GG genotype patients(35.30％)was significantly lower than that in GA genotype group(56.60％,P<0.01),with statistically significant difference.The median ADP-PAG in poor metabolizers(58.40％)was significantly higher than that in intermediate metabolizers(42.05％,P<0.01),rapid metabolizers(29.80％,P<0.01),and ultra metabolizers(28.00％,P<0.05),and the median ADP-PAG in intermediate metabolizers was significantly higher than that in rapid metabolizers(P<0.01),with statistically significant differences.Significant differences were observed in the abnormal rate of INR among CYP2C19 2 GG(1.25％),GA(4.73％),and AA(7.81％)genotypes,with statistically significant difference(P=0.01).Multivariate Logistic regression analysis revealed that age(OR=0.98,P=0.01)and comorbid hypertension(OR=2.05,P=0.01)were independent factors influencing the risk of readmission due to IS recurrence within 1 year.Kaplan-Meier survival curve analysis showed that relapse-free survival time was significantly shorter in patients<70 years(P<0.01),with hypertension(P=0.02),and with CYP2C19 ultra-rapid metabolizers(P=0.02).CONCLUSIONS:CYP2C19 gene polymorphisms significantly affect the efficacy of antiplatelet drugs and coagulation function.The detection of CYP2C19 gene has important potential application value in individualized treatment of IS patients.