激素抵抗型支气管哮喘患者外周血MIB1基因甲基化的相关性研究

Correlation of MIB1 gene methylation in peripheral blood of patients with hormone resistant bronchial asthma

目的分析激素抵抗型支气管哮喘(哮喘)及普通哮喘患者外周血MIB1基因甲基化与糖皮质激素反应的相关性。方法使用前瞻性病例对照研究。收集2017年1月至2019年1月就诊于新疆维吾尔自治区人民医院呼吸与危重症医学中心的20例激素抵抗型哮喘患者、20例普通哮喘患者及20名健康体检者的外周血进行MIB1基因CpG_1、CpG_2、CpG_3位点的甲基化率检测,分析是否存在差异。随后对激素抵抗型哮喘及普通哮喘患者的临床特征(发病年龄、体质量指数、血嗜酸粒细胞计数、血中性粒细胞计数)及CpG_1、CpG_2、CpG_3位点甲基化率进行危险因素的相关性分析。结果3组间两两比较MIB1基因3个位点的甲基化率,差异均无统计学意义(χ2=1.591、0.546、0.282,P值均>0.05)。二元Logistic回归分析显示CpG_1甲基化率和CpG_3甲基化率可能是哮喘患者发生激素抵抗的危险因素。激素抵抗型哮喘组与普通哮喘组间相关指标进行ROC曲线分析结果显示CpG_1甲基化率曲线下面积(AUC=0.734,约登指数1.478)优于CpG_3甲基化率曲线下面积(AUC=0.564,约登指数1.182)。结论CpG_1甲基化率及CpG_3甲基化率可能为哮喘患者发生激素抵抗的预测指标,且CpG_1甲基化率预测效能更优。

Objective To analyze the correlation between MIB1 gene methylation and glucocorticoid response in patients with hormone-resistant bronchial asthma(asthma)and general asthma.Methods Collect the peripheral blood of 60 cases(20 hormone-resistant asthma,20 general asthma,20 healthy medical examiners)who visited the Centre of Respiratory and Critical Care Medicine of the People′s Hospital of Autonomous Region from January 2017 to January 2019 to detect the methylation rate of MIB1 gene CpG_1,CpG_2,and CpG_3,and analysis the differences.And risk factors correlation analysis of clinical features(onset ages,body mass index,blood eosinophils,blood neutrophils)and CpG_1,CpG_2,CpG_3 methylation rate were taken.Results The methylation rates of three sites of MIB1 gene were pairwise compared among the three groups,and there was no statistically significant difference(χ2=1.591,0.546,0.282,all P>0.05).Binary Logistic regression analysis showed that methylation rate of CpG_1 and CpG_3 may be the risk factors of hormone resistance in asthmatic patients.ROC curve analysis showed that area under the curve(AUC)of CPG_1 methylation rate(AUC=0.734,Youden Index 1.478)was better than the AUC of CPG_3 methylation rate(AUC=0.564,Youden Index 1.182).Conclusions CPG_1 methylation rate and CPG_3 methylation rate may be the predictor of hormone resistance in asthmatic patients,and CPG_1 methylation rate is more effective in predicting hormone resistance.