组织蛋白酶Z基因启动子部分位点在成人哮喘中的差异性甲基化表达及意义

The significance of differential methylation expression of Cathepsin Z gene promoter in adult asthma

目的探讨组织蛋白酶Z基因(CTSZ)启动子区位点(cg01623438,cg02744249)在哮喘患者中的差异性甲基化表达及其与哮喘控制状态和肺功能的相关性,并探讨在成人哮喘诊断中的应用价值。方法选取于我院就诊的哮喘患者30例为哮喘组,根据哮喘控制评分将其分为三组,同时选取性别年龄匹配的同期健康体检成人30例为对照组。采集鼻黏膜上皮细胞,检测两位点甲基化水平并进行肺功能相关性分析,绘制ROC曲线分析其诊断应用价值。结果哮喘组两位点甲基化水平均低于正常对照组,且哮喘未控制组中甲基化水平最低,部分控制组次之,控制组最高。甲基化水平与肺功能改变呈负相关。单位点cg01623438的ROC曲线分析示,曲线下面积(AUC)为0.806(95%CI:0.683~0.896),敏感性为100%,特异性为50%(P <0.000 1);单位点cg02744249分析示AUC为0.749(95%CI:0.620~0.852),敏感性为43.3%,特异性为100%(P=0.000 1);两位点联合分析示AUC为0.827(95%CI:0.707~0.912),敏感性为66.7%,特异性为83.3%(P <0.000 1)。结论哮喘患者CTSZ启动子区出现明显低甲基化修饰,且与哮喘控制情况及肺功能存在一定相关性,提示可能对成人哮喘患者的诊断具有一定价值。

Objective The purpose of this study was to detect methylation level of two sites(cg01623438,cg02744249)in Cathepsin Z gene(CTSZ)promoter and their correlation with asthma control and pulmonary function,and to detect the diagnostic value in adult asthma patients.Methods 30 asthma patients in our hospital were selected as asthma group,and they were divided into three groups according to Asthma Control Test Score.Meanwhile,30 healthy adults matched with gender and age were selected as control group.We detected the methylation levels of the two sites in nasal epithelium cells,and the correlation analysis was performed between methylation level and lung function.Meanwhile,ROC curve analysis was used to show the asthma-predictive value.Results Both sites in asthma patients were hypomethylated,and the methylation level increased gradually in poorly controlled group,well controlled group and completely controlled group.The changes were also negatively related to the changes of lung function.ROC curve analysis showed that,the AUC(area under the curve)of the site cg01623438 was0.806(95%CI:0.683~0.896),the sensitivity was 100%and the specificity was 50%,P<0.0001;as the site g02744249,the AUC was 0.749(95%CI:0.620~0.852),the sensitivity was 43.3%and specificity was 100%(P=0.0001);the combination of these two sites shows that the AUC was 0.827(95%CI:0.707~0.912),the sensitivity was 66.7%and specificity was 83.3%(P=0.0001).Conclusion The methylation level of CTSZ promoter was significantly different in asthma patients,and it was related to asthma control and lung function.It can be used as an objective bio-marker to the assistance of asthma diagnosis and a reflection of the changes of lung function.