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  本文關(guān)鍵詞： 腸道病毒71型 Toll樣受體3 γ-干擾素 基因多態(tài)性　出處：《青島大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:腸道病毒71型(enterovirus 71,EV71)為手足口病的主要病原體之一,感染后臨床表現(xiàn)各異,宿主的遺傳背景差異在EV71致病機(jī)制中起到重要作用。本項研究探討TLR3c.1377C/T位點基因多態(tài)性與EV71手足口病病情嚴(yán)重程度的關(guān)系,分析不同基因表型對EV71感染患病風(fēng)險的影響。方法:收集2014年9月至2015年10月期間青島地區(qū)的EV71檢測陽性的手足口病患兒177例,并記錄一般情況(性別、年齡)、臨床癥狀(包括發(fā)熱持續(xù)時間,精神癥狀、吐瀉情況及神經(jīng)系統(tǒng)、心肺查體的陽性體征)、相關(guān)實驗室檢查(如白細(xì)胞計數(shù)、C-反應(yīng)蛋白、肌酸激酶同工酶、谷丙轉(zhuǎn)氨酶和谷草轉(zhuǎn)氨酶),根據(jù)《手足口病診療指南(2010版)》病情的嚴(yán)重的不同將病例組分為輕癥組、重癥組;同時收集本地區(qū)同時期于兩院健康體檢的兒童225例作為對照組。提取外周血白細(xì)胞基因組DNA,采用改良的多重連接酶反應(yīng)(i MLDR)技術(shù)檢測EV71手足口病患兒及正常對照組兒童TLR3c.1377C/T的基因多態(tài)性。應(yīng)用酶聯(lián)免疫吸附法(ELISA)檢測各組血清IFN-γ,IL-4的水平。全部數(shù)據(jù)均采用SPSS16.0軟件進(jìn)行數(shù)據(jù)統(tǒng)計處理,以p0.05認(rèn)為有統(tǒng)計學(xué)差異。結(jié)果:1.TLR3c.1377C/T位點TT、CT及CC基因型分布頻率在EV71感染組(42.37%,44.63%,12.99%)與對照組(51.11%,36.89%,12.00%)比較中未見顯著性差異(P0.05),同樣T、C等位基因分布頻率在EV71感染組(64.69%,35.31%)與對照組(69.56%,30.44%)比較中仍無顯著統(tǒng)計學(xué)差異(P0.05,OR=1.2,95%CI0.9-1.7)。2.TLR3c.1377C/T位點TT基因型在EV71手足口病重癥組(17.95%)的頻率高于輕癥組(9.09%),其差異有顯著統(tǒng)計學(xué)差異(P0.05)。TLR3c.1377T等位基因在EV71手足口病重癥組(42.95%)的頻率明顯高于輕癥組(29.29%),差異仍有統(tǒng)計學(xué)差異(P0.05,OR=1.8,95%CI 1.2-2.8)。3.EV71手足口病患兒的發(fā)熱持續(xù)時間、白細(xì)胞計數(shù)、C-反應(yīng)蛋白、血糖等指標(biāo)在TLR3c.1377C/T各基因型間分布有統(tǒng)計學(xué)差異(p0.05),TT基因型患兒以上指標(biāo)均高于CT基因型及CC基因型攜帶患兒。而性別、年齡、肌酸激酶同工酶、谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶及病毒載量等指標(biāo)在各基因型分布頻率無顯著統(tǒng)計學(xué)差異(P0.05)。4.在EV71感染組中,血清IFN-γ水平在TT基因型(102.0±24.2 pg/m L,P0.01)、CT基因型(114.1±26.2 pg/m L,P0.05)手足口病患兒中顯著低于CC基因型(135.5±36.8 pg/m L),血清IL-4水平在TT基因型(7.3±1.7 pg/m L,P0.01)、CT基因型(6.4±1.3 pg/m L,P0.05)手足口病患兒中顯著高于CC基因型(5.5±1.3 pg/m L)。IFN-γ/IL-4比值在TT基因型(14.2±2.8,P0.001)、CT基因型(18.0±3.1,P0.001)患兒中明顯低于CC基因型(24.9±4.7)。5.EV71感染組中,血清IFN-γ、IL-4水平及IFN-γ/IL-4比值與EV71病毒載量間均無明顯相關(guān)性關(guān)系(P0.05)結(jié)論:1.TLR3c.1377C/T位點基因多態(tài)性可能與EV71感染易感性無關(guān)。2.TLR3c.1377TT基因型和CT基因型攜帶患兒在EV71感染時血清IFN-γ水平明顯低于CC基因型,可能更易發(fā)展為重癥。
[Abstract]:Objective: enterovirus 71 (EV71) is one of the major pathogens of hand, foot and mouth disease (HFMD). The genetic background difference of host plays an important role in the pathogenesis of EV71. This study is to investigate the relationship between TLR3c.1377C/T locus polymorphism and the severity of EV71 HFMD. . To analyze the effect of different gene phenotypes on the risk of EV71 infection. From September 2014 to October 2015, 177 cases of hand-foot-mouth disease with EV71 positive were collected. General conditions (sex, age, clinical symptoms, including duration of fever, mental symptoms, diarrhea and nervous system, positive signs of cardiopulmonary examination, and related laboratory tests, such as white blood cell count) were recorded. C- reactive protein, creatine kinase isoenzyme, alanine aminotransferase and alanine aminotransferase were divided into mild group and severe group according to the severe difference of the condition of hand, foot and mouth disease. At the same time, 225 healthy children in the same period were collected as the control group. The genomic DNA of peripheral blood leukocytes was extracted. Modified multiplex ligase reaction (MLDR). The polymorphism of TLR3c.1377C/T gene in children with hand, foot and mouth disease (EV71) and normal control group was detected by Elisa, and the serum IFN- 緯 was detected by enzyme linked immunosorbent assay (Elisa). The level of IL-4. All the data are processed by SPSS16.0 software. Results: 1. TLR3c.1377C / T locus TTCT and CC genotype frequency were 42.37% in EV71 infection group. There was no significant difference between the control group and the control group (51.1136.89 and 12.00), the same as T. The distribution frequency of C allele in EV71 infection group (64.69) and control group (69.56 and 30.44) still had no significant difference (P0.05). OR=1.2. The frequency of TT genotype at TLR3c.1377C / T locus was higher in EV71 HFMD group than in mild group (P < 0.05). 9.09). There was significant statistical difference in the frequency of P0.05N. TLR3c.1377T allele in severe EV71 hand-foot-mouth disease group (42.95). 29.29. There were still significant differences in the duration of fever and white blood cell count in children with HFMD with CI 1.2-2.8 and 3.EV71. The distribution of C-reactive protein and blood glucose in TLR3c.1377C/T genotypes was significantly different (p0.05). The above indexes in TT genotype were higher than those in CT genotype and CC genotype group, but gender, age, creatine kinase isoenzyme and alanine aminotransferase were higher than those in CT genotype and CC genotype group. There was no significant difference in the distribution frequency of glutamic oxaloacetic transaminase and viral load among different genotypes. The level of serum IFN- 緯 was 102.0 鹵24.2 pg/m / L in TT genotype and 114.1 鹵26.2 pg/m / L in CT genotype. P0.05) Hand-foot-mouth disease children were significantly lower than CC genotype (135.5 鹵36.8 pg/m / L). The serum IL-4 level in TT genotypes was 7.3 鹵1.7 pg/m / L and 6.4 鹵1.3 pg/m / L in CT genotypes. P0.05) in HFMD children, the ratio of CC genotype was significantly higher than that of CC genotype (5.5 鹵1.3 pg/m / L). The ratio of IFN- 緯 / IL-4 in TT genotype was 14.2 鹵2.8. P0.001 CT genotype was significantly lower in children with CC genotype (18.0 鹵3.1) than in CC genotype (24.9 鹵4.7). 5. EV71 infection group. Serum IFN- 緯. There was no significant correlation between IL-4 level, IFN- 緯 / IL-4 ratio and EV71 viral load (P0.05). Conclusion:. 1. Polymorphism of TLR3c.1377C- T locus gene may not be associated with susceptibility to EV71 infection. 2. TLR3c.1377TT genotype and CT genotype carry EV71 susceptibility in children. The serum IFN- 緯 level at the time of infection was significantly lower than that of CC genotype. It is more likely to develop into severe disease.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R725.1

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