CYP2C19基因多态性、血清NT-proBNP水平与急性脑梗死静脉溶栓预后不良的关系

Relationships of CYP2C19 gene polymorphism and serum NT-proBNP level with poor prognosis of intravenous thrombolysis in acute cerebral infarction

目的探讨CYP2C19基因多态性、血清N末端B型脑利钠肽前体(NT-proBNP)水平与急性脑梗死(ACI)患者静脉溶栓预后不良的关系。方法选择210例ACI患者,均行阿替普酶静脉溶栓治疗,治疗90 d后根据改良Rankin量表(mRS)评分将患者分为预后不良组(mRS评分≥3分)52例、预后良好组(mRS评分<3分)158例。治疗前采用实时荧光定量PCR法检测CYP2C19基因多态性,时间分辨荧光免疫层析法检测血清NT-proBNP。用Pearson或Spearman分析CYP2C19基因多态性、血清NT-proBNP水平与mRS评分的相关性;用多因素Logistic回归分析ACI患者静脉溶栓预后的影响因素;用受试者工作特征曲线分析CYP2C19基因多态性、血清NT-proBNP水平对ACI患者静脉溶栓预后不良的预测价值。结果预后不良组年龄、高血压比例、糖尿病比例、入院美国国立卫生研究所脑卒中(NIHSS)评分、空腹血糖水平高于预后良好组(P均<0.05)。预后不良组和预后良好组CYP2C19基因多态性比较差异有统计学意义(P<0.05),预后不良组血清NT-proBNP水平高于预后良好组(P<0.05)。ACI患者CYP2C19基因多态性(r_(s)=0.362)、血清NT-proBNP水平(r=0.426)与mRS评分均呈正相关(P均<0.05)。高NIHSS评分、CYP2C19基因慢代谢型、高血清NT-proBNP水平是ACI患者预后不良的危险因素(P均<0.05)。CYP2C19基因多态性、血清NT-proBNP水平单独及联合预测ACI患者静脉溶栓预后的曲线下面积分别为0.752、0.786、0.861,二者联合预测的曲线下面积高于单独预测(P均<0.05)。结论CYP2C19基因多态性和高水平NT-proBNP是ACI患者静脉溶栓预后不良的危险因素,二者联合对不良预后有较高的预测价值。

Objective To explore the relationships between CYP2C19 gene polymorphism,serum N-terminal Btype brain natriuretic peptide precursor(NT-proBNP)level,and poor prognosis of intravenous thrombolysis in patients with acute cerebral infarction(ACI).Methods A total of 210 patients with ACI were selected and treated with intrave⁃nous thrombolysis with alteplase.After 90 days of treatment,patients were divided into the poor prognosis group(mRS score≥3 points)of 52 cases and good prognosis group(mRS score<3 points)of 158 cases based on the modified Rankin Scale(mRS)score.Before treatment,real-time fluorescence quantitative PCR was used to detect CYP2C19 gene polymor⁃phism,and time-resolved fluorescence immunoassay was used to detect serum NT-proBNP.The correlations between CYP2C19 gene polymorphism,serum NT-proBNP level and mRS Score were analyzed by Pearson or Spearman.Multivari⁃ate Logistic regression was used to analyze the influencing factors for prognosis of intravenous thrombolysis in ACI patients.The predictive value of CYP2C19 gene polymorphism and serum NT-proBNP level in predicting the prognosis of intrave⁃nous thrombolysis in ACI patients was analyzed by receiver operating characteristic curves.Results The age,hyperten⁃sion ratio,diabetes ratio,National Institutes of Health Stroke(NIHSS)score at admission and fasting blood glucose level in the poor prognosis group were higher than those in the good prognosis group(all P<0.05).There was a statistically sig⁃nificant difference in CYP2C19 gene polymorphism between the poor prognosis group and the good prognosis group(P<0.05),and the serum NT-proBNP level in the poor prognosis group was higher than that in the good prognosis group(P<0.05).The CYP2C19 gene polymorphism(r_(s)=0.362)and serum NT-proBNP level(r=0.426)were positively correlated with mRS score in ACI patients(both P<0.05).High NIHSS score,CYP2C19 gene slow metabolism type,and high se⁃rum NT-proBNP levels were risk factors for poor prognosis in ACI patients(all P<0.05).The area under the curve of CYP2C19 gene polymorphism and serum NT-proBNP levels alone and in combination for the prognosis of intravenous thrombolysis in ACI patients was 0.752,0.786,and 0.861,respectively,and the area under the curve of the combina⁃tion of the two was higher than that of either alone(all P<0.05).Conclusion CYP2C19 gene polymorphism and high level of NT-proBNP are risk factors for poor prognosis in ACI patients undergoing intravenous thrombolysis,and the combi⁃nation of the two has higher predictive value for poor prognosis.