本文關(guān)鍵詞： 結(jié)核 肺 白細(xì)胞介素23 受體 多態(tài)性 單核苷酸 病例對(duì)照研究　出處：《安徽醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景:肺結(jié)核是由結(jié)核分枝桿菌感染而引起的慢性傳染性肺病,是結(jié)核病中最常見的一種。盡管全球范圍的結(jié)核病防治工作已經(jīng)開展多年,但全球每年仍有大量的結(jié)核病新發(fā)病例和死亡病例,而我國(guó)作為全球第二位的結(jié)核病高負(fù)擔(dān)國(guó),結(jié)核病已經(jīng)嚴(yán)重危害到我國(guó)人群健康,成為嚴(yán)峻的公共衛(wèi)生問(wèn)題。結(jié)核菌感染人體大多數(shù)多為隱性感染,是否發(fā)病取決于機(jī)體的免疫狀態(tài),IL-23在天然免疫和適應(yīng)性免疫中扮演了重要的角色,參與眾多與結(jié)核病發(fā)病相關(guān)的免疫反應(yīng),IL-23R的缺失和異�？芍苯佑绊懙綑C(jī)體對(duì)結(jié)核菌的免疫應(yīng)答,而遺傳因素與機(jī)體的免疫狀態(tài)密不可分。近年來(lái)IL-23R基因多態(tài)性與免疫相關(guān)疾病的關(guān)聯(lián)已經(jīng)被大量報(bào)道,證明了IL-23R基因異�？芍苯佑绊懙綑C(jī)體的免疫狀態(tài)從而導(dǎo)致發(fā)病,成為重要的致病因素。然而在結(jié)核病中,IL-23R基因多態(tài)性的研究卻很少,僅在突尼斯人和中國(guó)維族人中有報(bào)道,SNPs在不同人群中分布差異較大,在漢族人群中開展IL-23R基因多態(tài)性與結(jié)核病的關(guān)聯(lián)研究,對(duì)于掌握IL-23R在漢族人群中的分布狀況,保護(hù)易感人群和全面了解結(jié)核病發(fā)病的遺傳學(xué)機(jī)制,具有重要的意義。目的:探索白介素23受體(IL-23R)基因多態(tài)性在漢族人群中的分布,以及與肺結(jié)核發(fā)病之間的關(guān)聯(lián)。方法:選取2014年3月至2015年12月在首都醫(yī)科大學(xué)附屬北京胸科醫(yī)院所收治的肺結(jié)核住院患者作為病例組,共243例;選取北京市昌平區(qū)結(jié)核病防治所于2014年5-10月進(jìn)行結(jié)核病體檢的健康者作為對(duì)照組,共226名。HapMap數(shù)據(jù)庫(kù)篩信息通過(guò)Haploview軟件并結(jié)合文獻(xiàn)檢索選出9個(gè)IL-23R基因單核苷酸多態(tài)性(single nucleotide polymorphism,SNP)位點(diǎn)(rs3762318、rs11209026、rs10889657、rs10889677、rs6682925、rs1004819、rs11465804、rs2201841、rs7514847)作為待測(cè)位點(diǎn),利用高溫連接酶檢測(cè)技術(shù)對(duì)待測(cè)位點(diǎn)進(jìn)行檢測(cè)并做基因分型,比較病例組和對(duì)照組等位基因及基因型頻率,分析找出連鎖不平衡和易感單倍型,從而發(fā)現(xiàn)該基因多態(tài)性與肺結(jié)核易感性之間的關(guān)系。結(jié)果:經(jīng)過(guò)比較分析,病例組和對(duì)照組在年齡,性別,婚姻狀況,文化程度上差異均無(wú)統(tǒng)計(jì)學(xué)意義P0.05;IL-23R多態(tài)性位點(diǎn)rs6682925最小等位基因C在病例組中頻率為44.0%(213/484),高于對(duì)照組中的37.4%(169/452),差異有統(tǒng)計(jì)學(xué)意義[χ2=4.24,P=0.040;OR(95%CI)值:1.21(1.01-1.71)];基因型TT在病例組頻率為30.1%(73/242),低于對(duì)照組的38.9%(88/226),差異有統(tǒng)計(jì)學(xué)意義[χ2=3.99,P=0.040;OR(95%CI)值:0.89(0.46-1.57)]。rs3762318等位基因C頻率在病例組中為16.0%(78/486),高于對(duì)照組的10.2%(46/450),差異有統(tǒng)計(jì)學(xué)意義[χ2=7.04,P0.01;OR(95%CI)值:1.68(1.13-2.49)];基因型CC在病例組中頻率為3.3%(8/243),高于對(duì)照組的0.4%(1/225),差異有統(tǒng)計(jì)學(xué)意義[χ2=5.02,P=0.040;OR(95%CI)值:7.58(0.92-60.20)];基因型TT頻率在病例組中為71.5%(173/243),低于對(duì)照組的80.0%(180/225),差異有統(tǒng)計(jì)學(xué)意義[χ2=4.89,P=0.030;OR(95%CI)值:0.84(0.39-0.95)]。連鎖分析和單倍型分析中發(fā)現(xiàn)由9個(gè)目標(biāo)SNP位點(diǎn)構(gòu)建的單倍型C T C A C T C T G在病例組中期望頻率為5.1%,在對(duì)照組中為2.2%,差異有統(tǒng)計(jì)學(xué)意義[χ2=5.65,P=0.02;OR(95%CI)值:2.44(1.14-5.19)];構(gòu)建單倍型域Block(rs3762318,rs10889657,rs6682925),發(fā)現(xiàn)單體型T T T在病例組和對(duì)照組中期望頻率為55.7%和61.3%,兩者差異有統(tǒng)計(jì)學(xué)意義[χ2=4.38,P=0.036;OR(95%CI)值:0.75(0.58-0.98)]。結(jié)論:rs6682925和rs3762318兩個(gè)多態(tài)性位點(diǎn)的突變?cè)跐h族人群中有較高的頻率,且和肺結(jié)核發(fā)病相關(guān),單倍型C T C A C T C T G是肺結(jié)核發(fā)病的危險(xiǎn)因素,構(gòu)建單倍型域發(fā)現(xiàn)單倍型T T T為肺結(jié)核發(fā)病的保護(hù)因素。
[Abstract]:Background: tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis infection, is one of the most common tuberculosis. Although TB worldwide have been carried out for many years, but every year there are still a lot of new TB cases and deaths, and China as the world's second TB high burden countries tuberculosis, has serious harm to our health, become a public health problem of severe tuberculosis infection. Most of the body is recessive infection, whether the incidence depends on the immune status, IL-23 plays an important role in innate immunity and adaptive immunity, in numerous associated with tuberculosis immune response, and loss of IL-23R the abnormal can directly affect the immune response to Mycobacterium tuberculosis, and genetic factors and immune status of the body are inseparable. In recent years, IL-23R gene polymorphism Associated with the immune related diseases have been reported, showed that the IL-23R gene abnormalities can directly affect the body's immune status and the cause of a disease, become an important pathogenic factor in tuberculosis. However, the polymorphisms of IL-23R gene was rarely reported only in Tunisia and Chinese Uighurs, SNPs in different populations the distribution difference in association between IL-23R gene polymorphism and tuberculosis in Chinese Han population, the distribution of master IL-23R in the Chinese Han population, susceptible population and a comprehensive understanding of the genetic mechanism of tuberculosis protection is of great significance. Objective: To explore the role of interleukin 23 receptor (IL-23R) gene polymorphism in distribution in the Chinese Han population, and the association between the incidence of pulmonary tuberculosis. Methods: from March 2014 to December 2015 in Beijing Thoracic Hospital affiliated to Capital Medical University from Pulmonary tuberculosis patients as case group, 243 cases; selection of TB control in Changping District of Beijing city in 2014 5-10 months of tuberculosis of healthy persons as control group, a total of 226.HapMap database screen information through Haploview software and combining with the literature retrieval selected 9 single nucleotide polymorphisms in the IL-23R gene (single nucleotide polymorphism, (SNP). Rs3762318, rs11209026, rs10889657, rs10889677, rs6682925, rs1004819, rs11465804, rs2201841, rs7514847) as the site to be measured, using the ligase detection technique to test sites by detecting and genotyping, between case group and control group genotype and allele frequency analysis, find out the linkage disequilibrium and haplotype susceptible to. Found the relationship between the gene polymorphism and susceptibility to pulmonary tuberculosis. Results: through comparative analysis, case group and control group in age, sex, marriage 濮葷姸鍐，

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