基于防御素家族DEFA1/DEFA3基因拷贝数多态性构建重症患者HAP风险预警模型的可行性

Feasibility of developing HAP risk warning model in critically ill patients based on genomic copy number polymorphisms of DEFA1/DEFA3

目的 评价基于防御素家族DEFA 1/DEFA3基因拷贝数多态性构建重症患者医院获得性肺炎（HAP）风险预警模型的可行性.方法 选择本院ICU内HAP患者（HAP组）77例,并以性别、年龄匹配的非HAP的ICU患者（NHAP组）109例.采集外周血标本提取DNA,采用实时定量PCR法检测DEFA 1/DEFA3基因拷贝数多态性.记录患者来源、人ICU 24 h内气管插管情况、入ICU24 h内最高急性生理情况评分、急性生理及慢性健康状况评分、序贯脏器衰竭评分,记录机械通气时间、住院时间、ICU停留时间以及转归.结合DEFA1/DEFA3基因拷贝数与入ICU 24 h内的临床因素（急性生理情况评分与急诊来源）,应用logistic回归建立预测模型.应用受试者工作特征曲线评价模型预测效能.结果 HAP组DEFA 1/DEFA3基因拷贝数明显低于NHAP组（P＜0.05）.结合DE-FA1/DEFA3基因拷贝数与入ICU 24 h内的临床因素建立的HAP预测模型,其预测HAP的受试者工作特征曲线下面积为0.789（95％可信区间0.724～0.854）.结论 防御素家族DEFA1/DEFA3基因拷贝数多态性可用于构建重症患者HAP的风险预警模型.

Objective To evaluate the feasibility of developing hospital acquired pneumonia （HAP） risk warning model in critically ill patients based on genomic copy number polymorphisms （CNPs） of the genes encoding human neutrophil peptides 1-3 （DEFA1/DEFA3）.Methods Seventy-seven HAP patients （group HAP） and 109 non-HAP patients of matched age and sex in intensive care unit （ICU） （group NHAP） were enrolled in the study.The genomic CNPs of DEFA1/DEFA3 was determined by realtime quantitative polymerase chain reaction after extracting DNA from peripheral blood samples.The source of patients,condition of endotracheal intubation within 24 h after admission to ICU,Acute Physiology Score,Acute Physiology and Chronic Health Evaluation Ⅱ score,Sequential Organ Failure Assessment score,mechanical ventilation time,length of hospital and ICU stay and outcomes were obtained.The predictive model was developed using logistic regression through combining DEFA1/DEFA3 copy numbers and clinical characteristics （Acute Physiology Score and source of emergency） within 24 h after admission to ICU.The receiver operating characteristic curve was used to evaluate the predictive efficacy of the model.Results The copy numbers of DEFA1/DEFA3 were significantly lower in HAP group than in NHAP group （P 〈0.05）.The area under the receiver operating characteristic curve of the predictive model developed through combining the DEFA1/DEFA3 copy numbers with clinical characteristics was 0.789 （95% CI 0.724-0.854） when the model was used for predicting HAP.Conclusion CNPs of DEFA1/DEFA3 can be used to develop the HAP risk warning model in critically ill patients.