关键词: 细胞色素P450 2C19, 基因多态性, miR-374b-5p, 急性脑梗死, 神经功能缺损, 预后

Abstract:

Objective To investigate the relationship between cytochrome P450 2C19（CYP2C19） polymorphism，serum miR-374b-5p level with neurological impairment and short-term prognosis in patients with acute cerebral infarction（ACI）. Methods A total of 164 ACI patients admitted to Zhengzhou Seventh People's Hospital from January 2019 to December 2022 were enrolled. The general data of all the patients were collected，and CYP2C19 genotype and serum miR-374b-5p relative expression levels were determined. The National Institutes of Health Stroke Scale（NIHSS） was used to evaluate the degree of neurological impairment in ACI patients. According to the NIHSS score after 15 d of treatment，the ACI patients were classified into good prognosis group and poor prognosis group. Spearman correlation analysis was used to evaluate the correlation between serum miR-374b-5p and NIHSS score at admission. Multivariate Logistic regression analysis was used to evaluate the risk factors for poor short-term prognosis in ACI patients. The efficacy of CYP2C19 genotype and serum miR-374b-5p in determining the short-term prognosis of patients with ACI was evaluated by receiver operating characteristic（ROC） curve. Results Among the 164 ACI patients with CYP2C19 genotype，there were 26 cases（15.86%） of GG type（wild homozygote），66 cases（40.24%） of GA type（mutant heterozygote） and 72 cases（43.90%） of AA type（mutant homozygote）. The allele frequency of A was 64.02%，and the allele frequency of G was 35.98%. Genotype distribution was consistent with Hardy-Weinberg equilibrium law（χ²=2.620，P=0.106）. The NIHSS scores of GG genotype，GA genotype and AA genotype were increased in turn on admission（P<0.001）. The relative expression level of serum miR-374b-5p was negatively correlated with the NIHSS score on admission（r_s=-0.510，P<0.001）. The incidence of poor prognosis in ACI patients was 19.51%（32/164）. There was statistical significance in age，infarct volume，time from onset to treatment，white blood cell（WBC） count，proportion of CYP2C19 AA genotype and relative expression level of serum miR-374b-5p between good and poor prognosis groups（P<0.05）. Infarct volume，time from onset to treatment，WBC count and CYP2C19 AA genotype were all risk factors for poor prognosis in ACI patients（P<0.05），and the relative expression level of miR-374b-5p was protective factor（P=0.007）. The areas under curves（AUC） of AA genotype and serum miR-374b-5p for determining poor prognosis of ACI patients were 0.631，0.730 and 0.802，respectively. Conclusions Both CYP2C19 polymorphism and serum miR-374b-5p relative expression level are related with neurological impairment in ACI patients，which can be used as the indicators of short-term prognosis in ACI patients.

Key words: Cytochrome P450 2C19, Gene polymorphism, MiR-374b-5p, Acute cerebral infarction, Neurological impairment, Prognosis