医学研究生学报
醫學研究生學報
의학연구생학보
JOURNAL OF MEDICAL POSTGRADUATE
2015年
9期
944-948
,共5页
陈晨%徐小勇%谢浩%孙辉明%陈菲%方明%赵蓓蕾
陳晨%徐小勇%謝浩%孫輝明%陳菲%方明%趙蓓蕾
진신%서소용%사호%손휘명%진비%방명%조배뢰
侵袭性曲霉病%Toll样受体4%基因测序%基因变异
侵襲性麯黴病%Toll樣受體4%基因測序%基因變異
침습성곡매병%Toll양수체4%기인측서%기인변이
Invasive aspergillosis%Toll-like receptor 4%Genetic sequencing%Genetic variation
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 GenBank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 C>G和1420 C>T,均为错义突变。蛋白结构预测结果显示219 C>G突变导致TLR4识别病原体的功能区改变,TLR41420 C>T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(219C>G与1420C>T),该基因的突变可能增加机体对IA的易感性。
目的: Toll樣受體( Toll-like receptors, TLRs)傢族是最重要的病原識彆受體,動物實驗髮現TLR4-/-小鼠更容易感染麯黴。文中探討我國漢族人群TLR4基因編碼區變異情況以及該基因變異與侵襲性麯黴病( invasive aspergillosis, IA)易感性的關繫。方法迴顧性收集2011年6月至2012年12月南京軍區南京總醫院確診為IA的25例住院患者設為IA組,其中男性17例,平均年齡(52.4±12.3)歲,有基礎疾病12例、無基礎疾病的13例;健康體檢者103例設為對照組,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。採集研究對象外週靜脈血,提取外週血中DNA,採用聚閤酶鏈式反應( PCR)擴增TLR4基因編碼區序列後測序,測序結果與NCBI GenBank中的TLR4編碼序列進行比對,併分析基因突變引起的氨基痠改變以及對蛋白質功能的影響。比較IA組與對照組TLR4基因突變率的差異。結果研究共髮現2箇突變點,分彆為219 C>G和1420 C>T,均為錯義突變。蛋白結構預測結果顯示219 C>G突變導緻TLR4識彆病原體的功能區改變,TLR41420 C>T未引起結構域改變。 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疾病;對照組未髮現突變,2組間比較差異有統計學意義( P=0.037)。結論 IA患者存在TLR4基因編碼區錯義突變(219C>G與1420C>T),該基因的突變可能增加機體對IA的易感性。
목적: Toll양수체( Toll-like receptors, TLRs)가족시최중요적병원식별수체,동물실험발현TLR4-/-소서경용역감염곡매。문중탐토아국한족인군TLR4기인편마구변이정황이급해기인변이여침습성곡매병( invasive aspergillosis, IA)역감성적관계。방법회고성수집2011년6월지2012년12월남경군구남경총의원학진위IA적25례주원환자설위IA조,기중남성17례,평균년령(52.4±12.3)세,유기출질병12례、무기출질병적13례;건강체검자103례설위대조조,기중남성70례,평균년령(56.0±17.2)세。소유연구대상균래원우한족인군。채집연구대상외주정맥혈,제취외주혈중DNA,채용취합매련식반응( PCR)확증TLR4기인편마구서렬후측서,측서결과여NCBI GenBank중적TLR4편마서렬진행비대,병분석기인돌변인기적안기산개변이급대단백질공능적영향。비교IA조여대조조TLR4기인돌변솔적차이。결과연구공발현2개돌변점,분별위219 C>G화1420 C>T,균위착의돌변。단백결구예측결과현시219 C>G돌변도치TLR4식별병원체적공능구개변,TLR41420 C>T미인기결구역개변。 IA조TLR4적돌변빈솔위8%(2/25),2례TLR4기인돌변적환자균무기출질병;대조조미발현돌변,2조간비교차이유통계학의의( P=0.037)。결론 IA환자존재TLR4기인편마구착의돌변(219C>G여1420C>T),해기인적돌변가능증가궤체대IA적역감성。
Objective Toll-like receptor ( TLR) gene family is the most important pathogen recognition receptor and animal experiment have found TLR4 mice is inclined to infect aspergillosis ( IA) .The study was to investigate the variation of TLR4 gene in Chinese Han nationality and its relation with the susceptibility of IA. Methods 25 patients diagnosed with proven IA from June 2011 to December 2012 in our hospital were enrolled, among which 17 were males.Their average age was 52.4 ±12.3, and 12 pa-tients had underlying diseases, the others had no underlying diseases.The control group consisted of 103 normal persons, among which 70 were males.Their average age was 56.0 ±17.2.All of the subjects were Chinese Han population.DNA was extracted from periph-eral blood.Polymerase chain reaction ( PCR) was applied to amplify the coding sequence of TLR4 gene followed by sequencing.The sequencing result was compared with TLR4 coding sequence in NCBI GenBank along with the analysis on amino acid change caused by genetic mutation and its effect on protein function.Comparison analysis was made on genetic mutation rate between IA group and con-trol group. Results Two missense mutations,TLR4 219 C>G and 1420 C>T, were identified in TLR4.The prediction result of protein structure showed 219 C>G resulted in the change of functional area for TLR4 to recognize pathogen and 1420 C>T caused no change in domains.The variation rate of TLR4 in IA group was 8%( 2/25 ) and both the patients had no underlying diseases. No mutation has been founded in control group and the difference between two groups was of statistical significance (P=0.037). Conclusion Two missense mutations (219 C>G and 1420 C>T) have been detec-ted in encoding area of TLR4 gene of IA patients.Variation in the cod-ing region of TLR4 gene may increase the susceptibility to IA.