侵袭性曲霉病患者Toll样受体4基因变异的初步研究

发布时间：2018-01-19 00:10

本文关键词： 侵袭性曲霉病 Toll样受体基因测序基因变异　出处：《医学研究生学报》2015年09期 　论文类型：期刊论文

【摘要】：目的 Toll样受体(Toll-like receptors,TLRs)家族是最重要的病原识别受体,动物实验发现TLR4-/-小鼠更容易感染曲霉。文中探讨我国汉族人群TLR4基因编码区变异情况以及该基因变异与侵袭性曲霉病(invasive aspergillosis,IA)易感性的关系。方法回顾性收集2011年6月至2012年12月南京军区南京总医院确诊为IA的25例住院患者设为IA组,其中男性17例,平均年龄(52.4±12.3)岁,有基础疾病12例、无基础疾病的13例;健康体检者103例设为对照组,其中男性70例,平均年龄(56.0±17.2)岁。所有研究对象均来源于汉族人群。采集研究对象外周静脉血,提取外周血中DNA,采用聚合酶链式反应(PCR)扩增TLR4基因编码区序列后测序,测序结果与NCBI Gen Bank中的TLR4编码序列进行比对,并分析基因突变引起的氨基酸改变以及对蛋白质功能的影响。比较IA组与对照组TLR4基因突变率的差异。结果研究共发现2个突变点,分别为219 CG和1420 CT,均为错义突变。蛋白结构预测结果显示219 CG突变导致TLR4识别病原体的功能区改变,TLR4 1420 CT未引起结构域改变。IA组TLR4的突变频率为8%(2/25),2例TLR4基因突变的患者均无基础疾病;对照组未发现突变,2组间比较差异有统计学意义(P=0.037)。结论 IA患者存在TLR4基因编码区错义突变(219CG与1420CT),该基因的突变可能增加机体对IA的易感性。
[Abstract]:Objective Toll-like receptor TLRsfamily is the most important pathogen recognition receptor. Animal experiments showed that TLR4-r-mice were more susceptible to Aspergillus. The variation of the coding region of TLR4 gene and the relationship between TLR4-r-mice and invasive aspergillosis (TLR4-r-mice) were studied in this paper. Invasive aspergillosis. Methods from June 2011 to December 2012, 25 inpatients diagnosed as IA in Nanjing General Hospital of Nanjing military region were divided into IA group (17 males). The average age was 52.4 卤12.3 years old. There were 12 cases with basic diseases and 13 cases with no underlying diseases. 103 healthy subjects were divided into control group (70 males, mean age 56.0 卤17.2). All the subjects were from Han nationality. Peripheral venous blood was collected from the subjects. TLR4 gene coding region was amplified by polymerase chain reaction (PCR) and sequenced. The sequencing results were compared with the TLR4 coding sequence in NCBI Gen Bank. The amino acid changes caused by gene mutation and the effect on protein function were analyzed. The difference of mutation rate of TLR4 gene between IA group and control group was compared. 219CG and 1420 CTs were missense mutations, respectively. The predicted protein structure showed that 219CG mutation resulted in the alteration of the functional region of TLR4 to recognize pathogens. TLR4 1420 CT did not cause structural domain change. The mutation frequency of TLR4 in IA group was 80.The mutation frequency of TLR4 gene in 2 patients with TLR4 gene mutation was 80.There were no underlying diseases. There was no significant difference between the two groups in the control group. Conclusion there is a missense mutation in the coding region of TLR4 gene in IA patients (219CG and 1420CTA). Mutations in the gene may increase the body's susceptibility to IA.
【作者单位】：南京军区南京总医院呼吸与危重症医学科;东南大学生命科学研究院发育与疾病相关基因教育部重点实验室;
【基金】：江苏省“六大人才高峰”资助项目(2011-WS-078)
【分类号】：R519.8
【正文快照】： 0引言侵袭性曲霉病(invasive aspergillosis,IA)是一种严重的感染性疾病,主要累及肺,且也可侵犯其他器官。该病常危及生命,病死率高达40%~90%[1-2]。IA多见于有粒细胞缺乏症、器官移植、长期使用糖皮质激素等危险因素的免疫缺陷患者,但临床中也发现IA可发生于无任何基础疾病的

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