MTHFR基因多态性对脑梗死患者阿替普酶静脉溶栓后出血性转化的影响

Effect of MTHFR gene polymorphism on hemorrhagic transformation after intravenous thrombolysis with alteplase in patients with cerebral infarction

摘要:

目的 分析亚甲基四氢叶酸还原酶（MTHFR）基因多态性对脑梗死患者阿替普酶静脉溶栓后出血性转化（HT）的影响。方法 回顾性分析2020年7月—2023年7月在安徽医科大学附属阜阳人民医院接受治疗的120例脑梗死患者的临床资料。依据治疗后24～72 h HT发生情况分为HT组（15例）、无HT组（105例）。比较两组基线资料、MTHFR基因多态性、纤维蛋白原（Fib）、同型半胱氨酸（Hcy）。采用多因素一般Logistic回归模型分析脑梗死患者阿替普酶静脉溶栓后HT发生的危险因素。绘制受试者工作特征（ROC）曲线，分析入院时美国国立卫生院卒中量表（NIHSS）评分、Hcy预测脑梗死患者阿替普酶静脉溶栓后HT发生的价值。结果 HT组心房颤动发生率、MTHFR基因型677CT占比、入院时NIHSS评分、Hcy水平均高于无HT组（P <0.05）。多因素一般Logistic回归分析结果显示：心房颤动史［O^R=1.478（95% CI：1.126，1.940）］、入院时NIHSS评分升高［O^R=1.656（95% CI：1.125，2.438）］、MTHFR基因型为677CT ［O^R=1.871/2.362（95% CI：1.052，3.328/1.081，4.652）］、Hcy水平升高［O^R=2.149（95% CI：1.108，4.168）］均为脑梗死患者阿替普酶静脉溶栓后HT发生的危险因素（P <0.05）。ROC曲线分析结果显示，入院时NIHSS评分、Hcy均可预测脑梗死患者阿替普酶静脉溶栓后HT发生，其敏感性分别为80.0%（95% CI：0.765，0.883）、73.3%（95% CI：0.717，0.834），特异性分别为74.3%（95% CI：0.659，0.817）、74.3%（95% CI：0.824，0.931）。677CT型患者Hcy水平高于677CC、677TT型患者（P <0.05）。结论 心房颤动、MTHFR基因型、入院时NIHSS评分、Hcy均为影响脑梗死患者阿替普酶静脉溶栓后HT发生的重要因素，临床应结合以上指标对高危患者进行重点筛查，尽早采取干预措施。

Abstract:

Objective To analyze the effect of methylene tetrahydrofolate reductase (MTHFR) gene polymorphism on hemorrhagic transformation (HT) after intravenous thrombolysis with alteplase in patients with cerebral infarction.Methods The clinical data of 120 patients with cerebral infarction who received treatment in Fuyang People's Hospital of Anhui Medical University from July 2020 to July 2023 were retrospectively analyzed. The patients were divided into HT group (n = 15) and non-HT group (n = 105) according to the occurrence of HT 24 to 72 hours after the treatment. The baseline data, MTHFR gene polymorphisms and levels of fibrinogen (Fib) and homocysteine (Hcy) of the two groups were compared. Multivariable Logistic regression analysis was performed to determine the risk factors for HT after intravenous thrombolysis with alteplase in patients with cerebral infarction. The value of National Institutes of Health Stroke Scale (NIHSS) score at admission and that of the level of Hcy in predicting HT in patients with cerebral infarction after intravenous thrombolysis with alteplase were analyzed by receiver operating characteristic (ROC) curves.Results The incidence of atrial fibrillation, the proportion of the MTHFR 677CT polymorphism, the NIHSS score at admission, and the level of Hcy were higher in the HT group than those in the non-HT group (P < 0.05). Multivariable Logistic regression analysis revealed that history of atrial fibrillation [O^R = 1.478 (95% CI: 1.126, 1.940) ], high NIHSS scores at admission [O^R = 1.656 (95% CI: 1.125, 2.438) ], MTHFR 677CT polymorphism [O^R = 1.871/2.362 (95% CI: 1.052, 3.328/1.081, 4.652) ], and increased levels of Hcy [O^R = 2.149 (95% CI: 1.108, 4.168) ] were risk factors for HT after intravenous thrombolysis with alteplase in patients with cerebral infarction (P < 0.05). ROC curve analysis confirmed that both NIHSS scores at admission and levels of Hcy could predict the occurrence of HT after intravenous thrombolysis with alteplase in patients with cerebral infarction, with sensitivities being 80.0% (95% CI: 0.765, 0.883) and 73.3% (95% CI: 0.717, 0.834), and specificities being 74.3% (95% CI: 0.659, 0.817) and 74.3% (95% CI: 0.824, 0.931). The level of Hcy in patients with MTHFR 677CT polymorphism was higher than that in those with MTHFR 677CC and 677TT polymorphisms (P < 0.05).Conclusions History of atrial fibrillation, MTHFR gene polymorphism, NIHSS scores at admission and levels of Hcy are all important factors affecting the occurrence of HT after intravenous thrombolytic therapy with alteplase in patients with cerebral infarction. These indicators should be included in clinical screening of high-risk patients to facilitate early intervention.