维生素D受体基因甲基化对泌尿道医院感染的影响

Methylation of vitamin D receptor gene and nosocomial urinary tract infection

目的探讨维生素D受体(Vitamin D receptor,VDR)基因甲基化对泌尿外科患者泌尿道医院感染的影响,为泌尿道医院感染的防控提出新的思路。方法选择2017年1月-2018年12月于福建医科大学附属第二医院泌尿外科住院治疗的患者454例为研究对象,根据泌尿道医院感染情况分为感染组186例和未感染组268例。采用高分辨率熔解曲线(High-resolution melting,HRM)法检测外周血VDR基因甲基化水平;分析患者性别、年龄、住院天数、泌尿道插管等情况,归纳泌尿外科患者泌尿道医院感染的影响因素及VDR基因甲基化对泌尿道感染的影响。结果感染组患者共检出菌株161株,其中革兰阴性菌119株占73.91%,革兰阳性菌33株占20.50%,真菌9株占5.59%,以大肠埃希菌、屎肠球菌、肺炎克雷伯菌、铜绿假单胞菌为主。不同检出菌的熔解温度(melting temperature,Tm)差异有统计学意义(P<0.05),革兰阴性菌的Tm值高于革兰阳性菌和真菌(P<0.05),而革兰阳性菌的Tm值与真菌差异无统计学意义(P=0.407)。感染组的Tm值为(70.20±0.20)℃低于对照组(P<0.001),感染组VDR基因甲基化程度低于对照组。多因素分析经调整人口学因素后,住院天数、泌尿道插管、联用抗菌药物是泌尿外科患者泌尿道医院感染的影响因素;VDR基因甲基化水平是泌尿道医院感染的保护因素(P<0.001)。结论VDR基因甲基化水平较高是泌尿道医院感染的保护因素,VDR基因甲基化在医院感染过程中发挥重要作用。

OBJECTIVE To investigate the influence of DNA methylation of vitamin D receptor on urinary tract nosocomial infection,and put forward new ideas for the prevention and control of urinary tract nosocomial infection.METHODS A total of 454patients hospitalized in the second affiliated Hospital of Fujian Medical University from Jan.2017to Dec.2018were divided into infection group(n=186)and non-infection group(n=268).The highresolution melting curve(HRM)was used to detect the DNA methylation level of VDR gene in peripheral blood and the Logitic multiple regression was used to analysis the influence of DNA methylation in vitamin D receptor gene to urinary tract nosocomial infection.Sex,age,length of stay and urinary intubation were analyzed.The influencing factors of urinary nosocomial infection in urological patients and the effect of VDR gene DNA methylation on urinary tract infection were summarized.RESULTS A total of 161strains were detected in the infection group,including 119strains of Gram-negative bacteria(73.91%),33strains of Gram-positive bacteria(20.50%)and 9strains of fungi(5.59%).The top bacteria detected in the infection group were Escherichia coli,Enterococcus faecium,Klebsiella pneumonia and Pseudomonas aeruginosa.The Tm values of different bacterial were significant(P<0.05).The Tm value of Gram-negative bacteria was significantly higher than that of Gram-positive bacteria and fungi(P<0.05),but there was no significant difference between Gram-positive bacteria and fungi(P=0.407).The Tm value in infected group was significantly lower than that in the control group(P<0.001),and the degree of DNA methylation in the infected group was lower than that in the control group.After adjusting demographic factors,long hospitalization days,urinary tract intubation,and combined use of antimicrobial drugs were the risk factors for urinary tract nosocomial infection.The level of methylation of VDR gene was a protective factor for urinary tract nosocomial infection(P<0.001).CONCLUTIONThe high level of VDR gene DNA methylation is the protective factor of urinary tract nosocomial infection.DNA methylation plays an important role in the process of nosocomial infection.