NRAMP1、Sp110基因多态性与肺结核易患相关性研究
发布时间：2019-04-02 18:37
【摘要】： 研究背景 肺结核病是由结核分枝杆菌引起的传染性疾病,个体因素对肺结核的发病有着重要影响,迄今为止,已发现多种基因多态与肺结核易患性相关。结核杆菌侵入机体后引起细胞免疫为主的免疫反应,巨噬细胞作为细胞免疫的重要组成部分,在肺结核的发病中起着重要作用。 本课题选取NRAMP1基因、Sp110基因均与巨噬细胞功能相关。NRAMP1(natural-resistance-associated macrophage protein 1,天然抗性相关性巨噬细胞蛋白1)可以作用于巨噬细胞吞噬体膜上的Fe2+和Mn2+等离子通道,使吞噬体内细菌或细胞二价阳离子摄入难度,最终被消化杀灭。NRAMP1基因多态性改变可能对NRAMP1蛋白功能产生影响,从而使机体免疫力改变,造成机体肺结核发病危险性增加。 Ipr1(intracellular pathogen resistance 1,细胞内病原体抵抗因子1)基因是最新发现的一种能调节小鼠结核病先天免疫力的新基因,人体中与Ipr1蛋白同源性最高的是核体蛋白Sp110b。Sp110蛋白可能与免疫功能相关,并且可以通过细胞核激素受体之间的信号传递,对控制巨噬细胞生命周期起着重要作用,因此Sp110基因可能是人体结核病易患性相关的一个新候选基因。目前关于Sp110基因的研究报道较少,相关研究主要集中在非洲西部,对中国人群的研究尚未见到报道。 NRAMP1、Sp110基因之间与肺结核易患性有无协同或者拮抗作用,值得我们深入研究。 目的 研究NRAMP1rs17235409A/G、NRAMP1rs17235416TGTG/(-),Sp110rs3948464C/T位点多态性与重庆地区汉族人群肺结核易患性的关系。综合分析NRAMP1基因和Sp110基因之间的交互作用,为采取有效的防治措施提供科学的依据。 方法 采用病例对照研究。病例来源于重庆市、区结核病防治所,按肺结核诊断标准(GB 15987-1995)所确诊的初治肺结核痰涂片阳性的汉族患者,共100例。对照为同样诊断标准排除肺结核等疾病的汉族正常人,共106例。用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法对NRAMP1基因rs17235409A/G、rs17235416TGTG/(-),和Sp110基因rs3948464C/T进行基因分型。采用χ2检验等统计方法分析这3个位点SNP与结核病易患性的关系,数据分析利用SAS8.2软件进行。结合前期试验结果,运用MDR(多因子降维分析法)软件对NRAMP1基因、Sp110基因交互作用进行分析。 结果 1. NRAMP1基因rs17235409病例组中GG、GA+AA基因型频率分别为67.00%、33.00%;对照组中分别为87.34%、12.26%,组间分布差异有统计学意义,χ2 =12.7567,P0.05。具有GA或/和AA基因型的个体患肺结核的OR为3.5235,OR95%CI为1.7427～7.0350。 NRAMP1rs17235416TGTG/(-)多态性基因频率在病例和对照组间有显著性差异,χ2 =7.41,P0.05。拥有TGTG/(-)+TGTG(-)/(-)基因型的个体的OR值为2.3402,OR95%CI为1.2688～4.3163, NRAMP1 rs17235409 GA和AA基因型、NRAMP1 rs17235416 TGTG/(-)和TGTG(-)/(-)基因型可能是肺结核发生的危险因素。 2. Sp110基因rs3948464 CC、CT基因型在病例组和对照组间的分布差异有统计学意义,χ2 =14.49,P0.05。具有rs3948464 CC基因型的OR值为4.3724,OR95%CI为2.0453～9.3474。Sp110 rs3948464CC基因型可能是肺结核的危险基因型的个体患肺结核的危险性是具有CT基因型个体的4.3724倍。 3. MDR软件进行交互作用分析,结果显示Sp110rs722555A/G、Sp110rs11679983A/G、Sp110rs 3948464C/T、NRAMP1rs17235409A/G 4个位点之间没有明显的交互作用。 结论 1. Sp110 rs3948464C/T、NRAMP1 rs17235409A/G及NRAMP1 rs17235416TGTG/(-)3位点多态性均与肺结核易患性相关,可能是重庆地区汉族人群肺结核易患性的影响因素。Sp110rs3948464C等位基因、NRAMP1rs17235409A等位基因、NRAMP1rs17235416 TGTG(-)等位基因可能是重庆市汉族人群肺结核发生的危险因素。 2. Sp110rs722555A/G、Sp110rs11679983A/G、Sp110rs 3948464C/T、NRAMP1rs17235409A/G 4个位点多态性之间没有明显的交互作用。 本研究是国内首次对Sp110基因rs3948464C/T多态性与肺结核易患相关性的研究,也是首次在重庆地区对NRAMP1基因多态性与肺结核易患相关性的研究。研究结果将为进一步阐明肺结核的发病机制、高危人群的预防以及药物研制奠定基础。
[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鍊间负2.3402,OR95%CI涓，
本文编号：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鍊间负2.3402,OR95%CI涓，
本文编号：2452810
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