基于全基因组关联分析的肾移植术后糖尿病发病风险预测模型的构建  

Construction of a risk prediction model for diabetes after kidney transplantation based on genome-wide association study

作　　者：王依娜 沈洲姬 奚炜炜[2] 诸医蒙 张孝认 仉超 裘晓蕙[1] 徐鹏杰[1] 胡雨韵 王江东 Wang Yina;Shen Zhouji;Xi Weiwei;Zhu Yimeng;Zhang Xiaoren;Zhang Chao;Qiu Xiaohui;Xu Pengjie;Hu Yuyun;Wang Jiangdong(Department of Nephrology,the Affiliated Lihuili Hospital,Ningbo University,Ningbo 315040,China;Department of Nephrology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310018,China;Department of Laboratory,the Affiliated Lihuili Hospital,Ningbo University,Ningbo 315040,China)

机构地区：[1]宁波大学附属李惠利医院肾内科,宁波315040 [2]浙江大学医学院附属邵逸夫医院肾内科,杭州310018 [3]宁波大学附属李惠利医院检验科,宁波315040

出　　处：《中华医学杂志》2024年第2期138-146,共9页National Medical Journal of China

基　　金：浙江省医药卫生科技计划项目(2023KY250)

摘　　要：目的探索肾移植术后糖尿病(PTDM)的临床危险因素及易感基因,构建PTDM发病风险预测模型。方法回顾性分析2001年1月至2022年12月期间在宁波大学附属李惠利医院和浙江大学医学院附属邵逸夫医院随访的肾移植受者资料,根据术后是否发生PTDM将其分为PTDM组和非PTDM组(Non-PTDM组),比较两组临床指标差异,筛选PTDM的危险因素,并通过全基因组关联分析(GWAS)筛选PTDM易感基因。分别建立仅基于临床指标(模型1)和临床指标结合易感基因(模型2)的PTDM发病风险预测模型,比较两种预测模型的预测效能。最后绘制较优模型的列线图,评价模型的校准度、区分度及临床实用性。结果纳入113例肾移植受者,男70例,女43例,年龄(46.2±10.8)岁。PTDM组51例,Non-PTDM组62例。通过GWAS和多因素logistic回归分析筛选出的相关因素包括糖尿病家族史(OR=88.912,95%CI:5.827~1356.601,P=0.001)、术前甘油三酯(OR=1.888,95%CI:1.150~3.098,P=0.012)、血尿酸(OR=1.011,95%CI:1.000~1.022,P=0.045)3个临床指标及rs802707基因位点(OR=10.046,95%CI:1.462~69.042,P=0.019)。模型1预测PTDM发生的受试者工作特征(ROC)曲线下面积(AUC)为0.891(95%CI:0.811~0.972),灵敏度为0.889,特异度为0.742;模型2预测PTDM发生的AUC为0.930(95%CI:0.864~0.995),灵敏度为0.885,特异度为0.900。结论糖尿病家族史、移植前甘油三酯、血尿酸这3个临床指标及rs802707基因位点与PTDM的发生有关联,联合易感基因能提高临床指标对PTDM发病风险的预测能力。Objective To explore the clinical risk factors and susceptibility genes of diabetes after kidney transplantation(PTDM)and construct a risk prediction model for PTDM.Methods The data of kidney transplant recipients who underwent follow-up in the Affiliated Lihuili Hospital,Ningbo University and Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from January 2001 to December 2022 were retrospectively analyzed.The recipients were divided into PTDM group and Non-PTDM group according to whether they were complicated with PTDM.The differences in clinical indicators between the two groups were compared,the risk factors affecting the incidence of PTDM were determined,and susceptibility genes of PTDM were screened by genome-wide association study(GWAS).PTDM risk prediction models based only on clinical indicators(Model 1)and clinical indicators combined with susceptibility genes(Model 2)were established respectively,and the predictive performance of the two prediction models was compared.Finally,the Nomogram of the optimal model was drawn,and the discrimination,calibration and clinical applicability of the model were evaluated.Results A total of 113 kidney transplant recipients(70 males and 43 females)were included,with an average age of(46.2±10.8)years.There were 51 cases in PTDM group and 62 cases in Non-PTDM group.The related factors screened by GWAS and logistic regression analysis included family history of diabetes(OR=88.912,95%CI:5.827-1356.601,P=0.001),preoperative triglyceride(TG)(OR=1.888,95%CI:1.150-3.098,P=0.012),uric acid(UA)(OR=1.011,95%CI:1.000-1.022,P=0.045)and rs802707(OR=10.046,95%CI:1.462-69.042,P=0.019).The area under the curve(AUC)of the receiver operating characteristics analysis(ROC)predicted by Model 1 for PTDM was 0.891(95%CI:0.811-0.972),with the sensitivity of 0.889 and the specificity of 0.742.The AUC of ROC curve predicted by Model 2 for PTDM was 0.930(95%CI:0.864-0.995),with the sensitivity of 0.885 and the specificity of 0.900.Conclusions Family history of diabetes,preoperativ

关 键 词：肾移植 移植后糖尿病 易感基因 危险因素 预测模型 

分 类 号：R699.2[医药卫生—泌尿科学] R587.1[医药卫生—外科学]