本文關(guān)鍵詞： 侵襲性曲霉病 Toll樣受體 基因測序 基因變異　出處：《醫(yī)學(xué)研究生學(xué)報》2015年09期 　論文類型：期刊論文

【摘要】：目的 Toll樣受體(Toll-like receptors,TLRs)家族是最重要的病原識別受體,動物實驗發(fā)現(xiàn)TLR4-/-小鼠更容易感染曲霉。文中探討我國漢族人群TLR4基因編碼區(qū)變異情況以及該基因變異與侵襲性曲霉病(invasive aspergillosis,IA)易感性的關(guān)系。方法回顧性收集2011年6月至2012年12月南京軍區(qū)南京總醫(yī)院確診為IA的25例住院患者設(shè)為IA組,其中男性17例,平均年齡(52.4±12.3)歲,有基礎(chǔ)疾病12例、無基礎(chǔ)疾病的13例;健康體檢者103例設(shè)為對照組,其中男性70例,平均年齡(56.0±17.2)歲。所有研究對象均來源于漢族人群。采集研究對象外周靜脈血,提取外周血中DNA,采用聚合酶鏈?zhǔn)椒磻?yīng)(PCR)擴(kuò)增TLR4基因編碼區(qū)序列后測序,測序結(jié)果與NCBI Gen Bank中的TLR4編碼序列進(jìn)行比對,并分析基因突變引起的氨基酸改變以及對蛋白質(zhì)功能的影響。比較IA組與對照組TLR4基因突變率的差異。結(jié)果研究共發(fā)現(xiàn)2個突變點(diǎn),分別為219 CG和1420 CT,均為錯義突變。蛋白結(jié)構(gòu)預(yù)測結(jié)果顯示219 CG突變導(dǎo)致TLR4識別病原體的功能區(qū)改變,TLR4 1420 CT未引起結(jié)構(gòu)域改變。IA組TLR4的突變頻率為8%(2/25),2例TLR4基因突變的患者均無基礎(chǔ)疾病;對照組未發(fā)現(xiàn)突變,2組間比較差異有統(tǒng)計學(xué)意義(P=0.037)。結(jié)論 IA患者存在TLR4基因編碼區(qū)錯義突變(219CG與1420CT),該基因的突變可能增加機(jī)體對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 鹵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 鹵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.
【作者單位】： 南京軍區(qū)南京總醫(yī)院呼吸與危重癥醫(yī)學(xué)科;東南大學(xué)生命科學(xué)研究院發(fā)育與疾病相關(guān)基因教育部重點(diǎn)實驗室;
【基金】：江蘇省“六大人才高峰”資助項目(2011-WS-078)
【分類號】：R519.8
【正文快照】： 0引言侵襲性曲霉病(invasive aspergillosis,IA)是一種嚴(yán)重的感染性疾病,主要累及肺,且也可侵犯其他器官。該病常危及生命,病死率高達(dá)40%~90%[1-2]。IA多見于有粒細(xì)胞缺乏癥、器官移植、長期使用糖皮質(zhì)激素等危險因素的免疫缺陷患者,但臨床中也發(fā)現(xiàn)IA可發(fā)生于無任何基礎(chǔ)疾病的

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1 江浩;趙蓓蕾;施毅;曹鄂洪;宋勇;張桂;孫文逵;;侵襲性肺曲霉病20例[J];中國感染與化療雜志;2009年04期

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