m^(6)A甲基化调节因子在慢性肾脏病中的预测价值  

The predictive value of m^(6)A methylation regulators in chronic kidney disease

作　　者：崔超群 张帆 李怡淳 张铁如 周涵 雷立健 CUI Chaoqun;ZHANG Fan;LI Yichun;ZHANG Tieru;ZHOU Han;LEI Lijian(Department of Epidemiology,School of Public Health,Shanxi Medical University,Taiyuan 030001,China;MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China;Research Centre of Environmental Pollution and Major Chronic Diseases Epidemiology,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学公共卫生学院流行病学教研室,太原030001 [2]煤炭环境致病与防治教育部重点实验室,太原030001 [3]山西医科大学环境污染与重大慢病流行病学研究中心,太原030001

出　　处：《中华疾病控制杂志》2024年第11期1336-1343,共8页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81872701)。

摘　　要：目的研究RNA N^(6)-甲基腺嘌呤(N^(6)-methyladenosine,m^(6)A)甲基化调节因子在慢性肾脏病(chronic kidney disease,CKD)中的表达变化,为疾病预防提供新的思路和靶点。方法选取中国华北地区某市社区人群作为研究对象,比较病例组(151人)和对照组(362人)基线特征,并分析RNA m^(6)A甲基化调节因子和肾功能指标的相关性,利用LASSO回归筛选相关变量用于构建多因素logistic回归分析模型;通过受试者工作特征曲线、校准曲线和决策曲线对模型进行验证。结果病例组中甲基转移酶样蛋白14(methyltransferase like 14,METTL14)表达水平更高(P<0.05),相关性分析结果显示,METTL14(r_(s)=-0.110,P<0.05)、去甲基化酶AlkB同源物5(human Alk B homolog 5,ALKBH5)(r_(s)=-0.218,P<0.001)均与转化生长因子(transforming growth factor,TGF)-β1呈负相关;脂肪量和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)与尿素(rs=0.169,P<0.001)、TGF-β1(r_(s)=0.088,P<0.05)均呈正相关。回归分析结果显示,性别、年龄、血肌酐、METTL14、总胆固醇和家庭人均月收入是CKD患病的预测因子(均P<0.05)。基于此构建风险预测模型,曲线下面积(area under curve,AUC)值为0.796(95%CI:0.752~0.840),Bootstrap法验证平均绝对误差值为0.036,通过Hosmer-Lemeshow拟合优度检验,预测模型有较好的校准能力(χ^(2)=12.57,P=0.128)。结论METTL14在CKD患者中表达水平较高,与CKD发生风险存在相关性。Objective To investigate in the expression changes of RNA N^(6)-methyladenosine(m^(6)A)methylation regulators in patients with chronic kidney disease(CKD)and provide novel ideas for disease prevention.Methods A community population in a city in North China was selected to compare the baseline characteristics between the case group(151)and control(362)group.The correlation between the expression of the regulators of RNA m6 A methylation and renal function-related indexes was analyzed.Screening of relevant variables for the construction of multivariable logistic regression models using LASSO regression,and its validity was assessed using the receiver operating characteristic curve(ROC),calibration curve and decision curve analysis(DCA).Results The expression level of methyltransferase like 14(METTL14)was higher in the case group(P<0.05).Correlation analysis revealed that METTL14(rs=-0.110,P<0.05)and human Alk B homolog 5(ALKBH5)(r_(s)=-0.218,P<0.001)were negatively correlated with transforming growth factor(TGF)-β1.Fat mass and obesity associated protein(FTO)was positively correlated with Urea(r_(s)=0.169,P<0.001)and TGF-β1(r_(s)=0.088,P<0.05).The regression analysis results indicated that gender,age,serum creatinine,METTL14,total cholesterol,and per capita monthly household income were predictors for CKD(all P<0.05).A risk prediction model was constructed based on this,and the area under the curve(AUC)was 0.796(95%CI:0.752-0.840).The average absolute error verified by bootstrap method was 0.036.The Hosmer Lemeshow goodness of fit test showed that the prediction model had good calibration ability(χ^(2)=12.57,P=0.128).Conclusions The expression level of METTL14 is higher in patients with CKD.There is a correlation between METTL14 and the development of CKD.

关 键 词：慢性肾脏病 RNA甲基化 列线图 LASSO回归 

分 类 号：R181[医药卫生—流行病学]