NRAMP1、Sp110基因多態(tài)性與肺結(jié)核易患相關(guān)性研究
發(fā)布時(shí)間：2019-04-02 18:37
【摘要】： 研究背景 肺結(jié)核病是由結(jié)核分枝桿菌引起的傳染性疾病,個(gè)體因素對(duì)肺結(jié)核的發(fā)病有著重要影響,迄今為止,已發(fā)現(xiàn)多種基因多態(tài)與肺結(jié)核易患性相關(guān)。結(jié)核桿菌侵入機(jī)體后引起細(xì)胞免疫為主的免疫反應(yīng),巨噬細(xì)胞作為細(xì)胞免疫的重要組成部分,在肺結(jié)核的發(fā)病中起著重要作用。 本課題選取NRAMP1基因、Sp110基因均與巨噬細(xì)胞功能相關(guān)。NRAMP1(natural-resistance-associated macrophage protein 1,天然抗性相關(guān)性巨噬細(xì)胞蛋白1)可以作用于巨噬細(xì)胞吞噬體膜上的Fe2+和Mn2+等離子通道,使吞噬體內(nèi)細(xì)菌或細(xì)胞二價(jià)陽(yáng)離子攝入難度,最終被消化殺滅。NRAMP1基因多態(tài)性改變可能對(duì)NRAMP1蛋白功能產(chǎn)生影響,從而使機(jī)體免疫力改變,造成機(jī)體肺結(jié)核發(fā)病危險(xiǎn)性增加。 Ipr1(intracellular pathogen resistance 1,細(xì)胞內(nèi)病原體抵抗因子1)基因是最新發(fā)現(xiàn)的一種能調(diào)節(jié)小鼠結(jié)核病先天免疫力的新基因,人體中與Ipr1蛋白同源性最高的是核體蛋白Sp110b。Sp110蛋白可能與免疫功能相關(guān),并且可以通過(guò)細(xì)胞核激素受體之間的信號(hào)傳遞,對(duì)控制巨噬細(xì)胞生命周期起著重要作用,因此Sp110基因可能是人體結(jié)核病易患性相關(guān)的一個(gè)新候選基因。目前關(guān)于Sp110基因的研究報(bào)道較少,相關(guān)研究主要集中在非洲西部,對(duì)中國(guó)人群的研究尚未見到報(bào)道。 NRAMP1、Sp110基因之間與肺結(jié)核易患性有無(wú)協(xié)同或者拮抗作用,值得我們深入研究。 目的 研究NRAMP1rs17235409A/G、NRAMP1rs17235416TGTG/(-),Sp110rs3948464C/T位點(diǎn)多態(tài)性與重慶地區(qū)漢族人群肺結(jié)核易患性的關(guān)系。綜合分析NRAMP1基因和Sp110基因之間的交互作用,為采取有效的防治措施提供科學(xué)的依據(jù)。 方法 采用病例對(duì)照研究。病例來(lái)源于重慶市、區(qū)結(jié)核病防治所,按肺結(jié)核診斷標(biāo)準(zhǔn)(GB 15987-1995)所確診的初治肺結(jié)核痰涂片陽(yáng)性的漢族患者,共100例。對(duì)照為同樣診斷標(biāo)準(zhǔn)排除肺結(jié)核等疾病的漢族正常人,共106例。用聚合酶鏈反應(yīng)-限制性片段長(zhǎng)度多態(tài)性(PCR-RFLP)的方法對(duì)NRAMP1基因rs17235409A/G、rs17235416TGTG/(-),和Sp110基因rs3948464C/T進(jìn)行基因分型。采用χ2檢驗(yàn)等統(tǒng)計(jì)方法分析這3個(gè)位點(diǎn)SNP與結(jié)核病易患性的關(guān)系,數(shù)據(jù)分析利用SAS8.2軟件進(jìn)行。結(jié)合前期試驗(yàn)結(jié)果,運(yùn)用MDR(多因子降維分析法)軟件對(duì)NRAMP1基因、Sp110基因交互作用進(jìn)行分析。 結(jié)果 1. NRAMP1基因rs17235409病例組中GG、GA+AA基因型頻率分別為67.00%、33.00%;對(duì)照組中分別為87.34%、12.26%,組間分布差異有統(tǒng)計(jì)學(xué)意義,χ2 =12.7567,P0.05。具有GA或/和AA基因型的個(gè)體患肺結(jié)核的OR為3.5235,OR95%CI為1.7427～7.0350。 NRAMP1rs17235416TGTG/(-)多態(tài)性基因頻率在病例和對(duì)照組間有顯著性差異,χ2 =7.41,P0.05。擁有TGTG/(-)+TGTG(-)/(-)基因型的個(gè)體的OR值為2.3402,OR95%CI為1.2688～4.3163, NRAMP1 rs17235409 GA和AA基因型、NRAMP1 rs17235416 TGTG/(-)和TGTG(-)/(-)基因型可能是肺結(jié)核發(fā)生的危險(xiǎn)因素。 2. Sp110基因rs3948464 CC、CT基因型在病例組和對(duì)照組間的分布差異有統(tǒng)計(jì)學(xué)意義,χ2 =14.49,P0.05。具有rs3948464 CC基因型的OR值為4.3724,OR95%CI為2.0453～9.3474。Sp110 rs3948464CC基因型可能是肺結(jié)核的危險(xiǎn)基因型的個(gè)體患肺結(jié)核的危險(xiǎn)性是具有CT基因型個(gè)體的4.3724倍。 3. MDR軟件進(jìn)行交互作用分析,結(jié)果顯示Sp110rs722555A/G、Sp110rs11679983A/G、Sp110rs 3948464C/T、NRAMP1rs17235409A/G 4個(gè)位點(diǎn)之間沒有明顯的交互作用。 結(jié)論 1. Sp110 rs3948464C/T、NRAMP1 rs17235409A/G及NRAMP1 rs17235416TGTG/(-)3位點(diǎn)多態(tài)性均與肺結(jié)核易患性相關(guān),可能是重慶地區(qū)漢族人群肺結(jié)核易患性的影響因素。Sp110rs3948464C等位基因、NRAMP1rs17235409A等位基因、NRAMP1rs17235416 TGTG(-)等位基因可能是重慶市漢族人群肺結(jié)核發(fā)生的危險(xiǎn)因素。 2. Sp110rs722555A/G、Sp110rs11679983A/G、Sp110rs 3948464C/T、NRAMP1rs17235409A/G 4個(gè)位點(diǎn)多態(tài)性之間沒有明顯的交互作用。 本研究是國(guó)內(nèi)首次對(duì)Sp110基因rs3948464C/T多態(tài)性與肺結(jié)核易患相關(guān)性的研究,也是首次在重慶地區(qū)對(duì)NRAMP1基因多態(tài)性與肺結(jié)核易患相關(guān)性的研究。研究結(jié)果將為進(jìn)一步闡明肺結(jié)核的發(fā)病機(jī)制、高危人群的預(yù)防以及藥物研制奠定基礎(chǔ)。
[Abstract]:Study Background Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The individual factors have an important influence on the pathogenesis of pulmonary tuberculosis. So far, it has been found that various gene polymorphism and tuberculosis are susceptible to infection. It is related to the immune response, which is the main part of cellular immunity, and plays an important role in the pathogenesis of pulmonary tuberculosis. The NRAMP1 gene and Sp110 gene were selected from the subject. NRAMP1 (natural resistance-related macrophage protein 1) can act on the ion channels such as Fe2 + and Mn2 + on the phagocytic membrane of the macrophage, The change of the polymorphism of the NRAMP1 gene may have an effect on the function of the NRAMP1 protein, so that the immunity of the body can be changed, and the pulmonary tuberculosis of the body can be caused. The risk is increased. Ipr1 (the internal pathogen resistance factor 1) gene is a new gene that can regulate the innate immunity of the mouse, and the highest homology with the Ipr1 protein in the human body is the core protein Sp110b. The Sp110 protein can can be related to the immune function and can be transmitted through the signal between the nuclear hormone receptors, which plays an important role in controlling the life cycle of the macrophages, so that the Sp110 gene may be related to the susceptibility to the human tuberculosis A new candidate gene is a new candidate. The current study on the Sp110 gene has been reported to be less, and the relevant research is mainly focused on the western part of Africa, and the research on the Chinese population It has not been reported that there is a synergistic or antagonistic relationship between the NRAMP1 and Sp110 genes and the susceptibility to tuberculosis. action For the purpose of studying the polymorphism of NRAMP1rs17235409A/ G, NRAMP1rs17235416TGTG/ (-) and Sp110rs3948464C/ T site. The relationship between the susceptibility of pulmonary tuberculosis in the Han population in Chongqing was analyzed. The interaction between the NRAMP1 gene and the Sp110 gene was comprehensively analyzed. to produce To take effective measures to prevent and cure The method is based on a case-control study. The case is derived from the tuberculosis diagnosis standard (GB 15987-1995) A total of 100 patients with positive pulmonary tuberculosis and sputum smear were diagnosed in the first group. The control was the same. The expression of rs17235409A/ G, rs17235416TGTG/ (-) of NRAMP1 gene, rs17235416TGTG/ (-), and Sp were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gene typing of the 110 gene rs3948464C/ T. The relationship between the vulnerability and the data is analyzed by SAS8.2 software. In combination with the earlier test results, the software of the MDR (multi-factor dimension reduction method) is applied to the N RA Results 1. The frequencies of GG, GA and AA in the 1. NRAMP1 gene rs17235409 were 67.00% and 33.00%, respectively, and 87.34% and 12.26% in the control group, respectively. The difference of the distribution among the groups was statistically significant, and the difference was 2 = 12.7567, P 0.05. The OR of the individual with the GA or/ and the AA genotype had pulmonary tuberculosis. For 3.5235, the OR95% CI is 1.7427-7.0350. NRAMP1rs17235416TGTG/ (-) polymorphism There was a significant difference in the frequency of the gene between the case and the control group,2 = 7.41, P0.5.05, and the individual with the TGTG/ (-) + TGTG (-)/ (-) genotype OR鍊間負(fù)2.3402,OR95%CI涓，
本文編號(hào)：2452810
[Abstract]:Study Background Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The individual factors have an important influence on the pathogenesis of pulmonary tuberculosis. So far, it has been found that various gene polymorphism and tuberculosis are susceptible to infection. It is related to the immune response, which is the main part of cellular immunity, and plays an important role in the pathogenesis of pulmonary tuberculosis. The NRAMP1 gene and Sp110 gene were selected from the subject. NRAMP1 (natural resistance-related macrophage protein 1) can act on the ion channels such as Fe2 + and Mn2 + on the phagocytic membrane of the macrophage, The change of the polymorphism of the NRAMP1 gene may have an effect on the function of the NRAMP1 protein, so that the immunity of the body can be changed, and the pulmonary tuberculosis of the body can be caused. The risk is increased. Ipr1 (the internal pathogen resistance factor 1) gene is a new gene that can regulate the innate immunity of the mouse, and the highest homology with the Ipr1 protein in the human body is the core protein Sp110b. The Sp110 protein can can be related to the immune function and can be transmitted through the signal between the nuclear hormone receptors, which plays an important role in controlling the life cycle of the macrophages, so that the Sp110 gene may be related to the susceptibility to the human tuberculosis A new candidate gene is a new candidate. The current study on the Sp110 gene has been reported to be less, and the relevant research is mainly focused on the western part of Africa, and the research on the Chinese population It has not been reported that there is a synergistic or antagonistic relationship between the NRAMP1 and Sp110 genes and the susceptibility to tuberculosis. action For the purpose of studying the polymorphism of NRAMP1rs17235409A/ G, NRAMP1rs17235416TGTG/ (-) and Sp110rs3948464C/ T site. The relationship between the susceptibility of pulmonary tuberculosis in the Han population in Chongqing was analyzed. The interaction between the NRAMP1 gene and the Sp110 gene was comprehensively analyzed. to produce To take effective measures to prevent and cure The method is based on a case-control study. The case is derived from the tuberculosis diagnosis standard (GB 15987-1995) A total of 100 patients with positive pulmonary tuberculosis and sputum smear were diagnosed in the first group. The control was the same. The expression of rs17235409A/ G, rs17235416TGTG/ (-) of NRAMP1 gene, rs17235416TGTG/ (-), and Sp were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gene typing of the 110 gene rs3948464C/ T. The relationship between the vulnerability and the data is analyzed by SAS8.2 software. In combination with the earlier test results, the software of the MDR (multi-factor dimension reduction method) is applied to the N RA Results 1. The frequencies of GG, GA and AA in the 1. NRAMP1 gene rs17235409 were 67.00% and 33.00%, respectively, and 87.34% and 12.26% in the control group, respectively. The difference of the distribution among the groups was statistically significant, and the difference was 2 = 12.7567, P 0.05. The OR of the individual with the GA or/ and the AA genotype had pulmonary tuberculosis. For 3.5235, the OR95% CI is 1.7427-7.0350. NRAMP1rs17235416TGTG/ (-) polymorphism There was a significant difference in the frequency of the gene between the case and the control group,2 = 7.41, P0.5.05, and the individual with the TGTG/ (-) + TGTG (-)/ (-) genotype OR鍊間負(fù)2.3402,OR95%CI涓，
本文編號(hào)：2452810
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