本文選題：肺結(jié)核(TB) + PRDM1-ATG5　； 參考：《第三軍醫(yī)大學(xué)》2014年碩士論文

【摘要】：結(jié)核病是一種可致死的嚴(yán)重傳染病，是人體感染結(jié)核分枝桿菌引起的，在人類歷史上曾導(dǎo)致重大疾病疫情。目前，據(jù)WHO最新報(bào)告統(tǒng)計(jì)的數(shù)據(jù)，全世界約有1/3人口、近20億人感染了結(jié)核菌，成為結(jié)核病菌的攜帶者。同時(shí)，每年至少新增800萬結(jié)核病患者，其中約1/3死于結(jié)核病，近45萬人發(fā)展為耐多藥結(jié)核病(MDR-TB)，17萬人死于MDR-TB。研究發(fā)現(xiàn)，大部分個(gè)體受到結(jié)核分枝桿菌感染后都將演變成潛伏性感染，在一定時(shí)間內(nèi)并不發(fā)病，其中除了個(gè)體營養(yǎng)水平及環(huán)境因素差異以外，遺傳因素在決定結(jié)核發(fā)病與否中起到了關(guān)鍵作用。 PRDM1(又名Blimp-1，位于人第6號染色體)，是一種在成熟B淋巴細(xì)胞發(fā)育為漿細(xì)胞時(shí)發(fā)揮重要作用轉(zhuǎn)錄因子，并能夠分泌一種抗體來增強(qiáng)機(jī)體的免疫應(yīng)答功能。巨噬細(xì)胞自噬及凋亡是結(jié)核分枝桿菌體內(nèi)清除的重要途徑，自噬相關(guān)基因ATG5，作為細(xì)胞自噬和凋亡的轉(zhuǎn)換開關(guān)，在自噬與凋亡的發(fā)生和發(fā)展過程中起重要的調(diào)控作用。ATG5直接參與了自噬泡的磷脂雙分子層延伸和封閉的2個(gè)重要環(huán)節(jié)，而自噬泡的形成是自噬現(xiàn)象發(fā)生的核心過程，也是到目前為止對自噬現(xiàn)象檢測和評價(jià)的重要指標(biāo)。近來有文獻(xiàn)報(bào)道，PRDM1-ATG5基因間的變異會影響PRDM1及ATG5的表達(dá)，進(jìn)而影響機(jī)體免疫應(yīng)答。因此，我們推測PRDM1-ATG5間基因多態(tài)性可能與結(jié)核感染存在相關(guān)性。 本研究試圖通過在中國西南漢族人群中搜集大量相關(guān)血液樣本，，開展結(jié)核易感性研究，驗(yàn)證位于基因PRDM1-ATG5之間rs548234位點(diǎn)及rs6937876位點(diǎn)的多態(tài)性與結(jié)核易感之間的關(guān)聯(lián)性，目的是在提高結(jié)核病預(yù)防、診斷、風(fēng)險(xiǎn)預(yù)測上取得進(jìn)展，為個(gè)體化醫(yī)療打下一定基礎(chǔ)。 該研究獲得以下主要實(shí)驗(yàn)結(jié)果： 1.搜集了251例結(jié)核組和294例對照組人群的外周血，提取基因組DNA后，通過PCR測序鑒定，其基因分型率為100%； 2.在整個(gè)研究人群中，rs548234位點(diǎn)、rs6937876位點(diǎn)在結(jié)核組和對照組中的基因型分布上均符合HWE平衡定律。rs548234位點(diǎn)及rs6937876位點(diǎn)單獨(dú)及聯(lián)合分析表明其與結(jié)核病的發(fā)生風(fēng)險(xiǎn)無遺傳學(xué)關(guān)聯(lián)； 3.在原發(fā)性肺結(jié)核組與對照組研究發(fā)現(xiàn)：rs6937876位點(diǎn)與原發(fā)性肺結(jié)核發(fā)生無顯著關(guān)聯(lián)；而rs548234位點(diǎn)與原發(fā)性肺結(jié)核發(fā)生顯著關(guān)聯(lián)，其中CC基因型頻率高于健康對照人群(CC vs. TT：OR=3.37，95%CI=1.498-7.579，p=0.003；CC vsCT+TT： OR=3.59，95%CI=1.642-7.848， p=0.001)；經(jīng)吸煙和城鎮(zhèn)差異校正后的Logistic回歸分析差異存在統(tǒng)計(jì)學(xué)意義(OR=1.532,95%CI=1.238-2.076，P=0.03)。 4.危險(xiǎn)因素分析表明：吸煙及城市化為結(jié)核發(fā)生的危險(xiǎn)因素(吸煙vs.不吸煙：OR=1.741,95%CI=1.189-2.547， p=0.004；城市vs.非城市： OR=1.638,95%CI=1.166-2.301，p=0.004)，而其他因素如年齡、飲酒及職業(yè)與結(jié)核發(fā)病無關(guān)聯(lián)。 綜上所述，在結(jié)核組和對照組中PRDM1-ATG5基因間rs548234位點(diǎn)和rs6937876位點(diǎn)的基因型分布均符合HWE平衡。在本研究所關(guān)注的人群中，rs548234及rs6937876多態(tài)性位點(diǎn)與結(jié)核病發(fā)生風(fēng)險(xiǎn)無顯著遺傳學(xué)關(guān)聯(lián)。 然而，其中一項(xiàng)數(shù)據(jù)顯示，在原發(fā)性肺結(jié)核病患者中，rs548234位點(diǎn)的CC基因型的頻率明顯高于健康對照人群，這提示rs548234C等位基因存在增加原發(fā)性肺結(jié)核病發(fā)生風(fēng)險(xiǎn)的可能性。因此，有理由推測，rs548234T/C多態(tài)性位點(diǎn)與中國西南地區(qū)漢族人群原發(fā)性肺結(jié)核病發(fā)病有關(guān)。
[Abstract]:Tuberculosis (TB) is a fatal and serious infectious disease, caused by Mycobacterium tuberculosis, which has caused major diseases in human history. At present, according to the data of the latest WHO report, there are about 1/3 population around the world, nearly 2 billion people are infected with TB bacteria and become carriers of tuberculosis bacteria. At the same time, at least 8 million new tuberculosis is added. About 1/3 of the patients, about 1/3 died of tuberculosis, nearly 450 thousand people developed to multidrug resistant tuberculosis (MDR-TB), and 170 thousand people died from MDR-TB. research. Most individuals will become latent infection after infection with Mycobacterium tuberculosis and are not ill for a certain period of time, in addition to the individual nutritional level and environmental factors, genetic factors It plays a key role in determining the incidence of tuberculosis.
PRDM1 (also known as Blimp-1, located on human chromosome sixth), is an important transcription factor in the development of a mature B lymphocyte as a plasma cell and can secrete an antibody to enhance the immune response function of the body. Macrophage autophagy and apoptosis are an important pathway for the clearance of Mycobacterium tuberculosis, as autophagy related gene ATG5. The conversion switch of autophagy and apoptosis plays an important role in the development and development of autophagy and apoptosis..ATG5 directly participates in the 2 important links of the phospholipid bimolecular layer extension and closure of autophagic vesicles, and the formation of autophagic bubbles is the core process of autophagy, and is also the test and evaluation of autophagy so far. It has been reported recently that the variation of PRDM1-ATG5 gene may affect the expression of PRDM1 and ATG5 and then affect the immune response of the body. Therefore, we speculate that the polymorphism of PRDM1-ATG5 gene may be associated with tuberculosis infection.
The purpose of this study is to verify the association between the polymorphism of the rs548234 and rs6937876 loci between PRDM1-ATG5 and the susceptibility to tuberculosis by collecting a large number of related blood samples in the Han population of Southwest China to verify the association between the polymorphism of the loci and rs6937876 loci between the gene and the susceptibility to tuberculosis. The purpose is to make progress in the prevention, diagnosis and risk prediction of tuberculosis. Physical medical treatment lays a foundation for it.
The study obtained the following main experimental results:
1. the peripheral blood of 251 cases of tuberculosis group and 294 cases of control group was collected. Genomic DNA was extracted and identified by PCR sequencing. The genotyping rate was 100%.
2. in the whole study population, the genotype distribution of rs548234 loci and rs6937876 loci in the tuberculosis group and the control group all conformed to the HWE equilibrium law.Rs548234 locus and the rs6937876 locus alone and in combination analysis showed that there was no genetic association with the risk of tuberculosis.
3. in the primary pulmonary tuberculosis group and the control group, there was no significant association between the rs6937876 locus and the primary pulmonary tuberculosis; the rs548234 locus was significantly associated with the primary pulmonary tuberculosis, and the CC genotype frequency was higher than that of the healthy controls (CC vs. TT:OR=3.37,95%CI= 1.498-7.579, p=0.003; CC vsCT+TT:OR=3.59,95%CI=1.642. -7.848, p=0.001); there was statistical significance in Logistic regression analysis after smoking and town difference correction (OR=1.532,95%CI=1.238-2.076, P=0.03).
4. analysis of risk factors showed that smoking and urbanization were risk factors for tuberculosis (smoking vs. non smoking: OR=1.741,95%CI=1.189-2.547, p=0.004; urban vs. non City: OR=1.638,95%CI=1.166-2.301, p=0.004), while other factors such as age, drinking and occupation were not associated with tuberculosis.
To sum up, the genotype distribution of the rs548234 and rs6937876 loci between the PRDM1-ATG5 gene and the rs6937876 loci in the tuberculosis group and the control group were all conformed to the HWE balance. There was no significant genetic association between the rs548234 and rs6937876 polymorphic loci and the risk of tuberculosis in the population of this study.
However, one of the data shows that in patients with primary pulmonary tuberculosis, the frequency of the CC genotype at the rs548234 site is significantly higher than that in healthy controls, suggesting the possibility of increasing the risk of primary pulmonary tuberculosis by rs548234C alleles. Therefore, there is reason to speculate that the rs548234T/C polymorphic loci are associated with the Han nationality in the southwest of China. The incidence of primary pulmonary tuberculosis in the population is related.

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R52

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

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