中国汉族人群中白介素23受体基因多态性与肺结核易感性关联的病例对照研究

发布时间：2018-01-22 10:36

  本文关键词： 结核 肺 白细胞介素23 受体 多态性 单核苷酸 病例对照研究　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:肺结核是由结核分枝杆菌感染而引起的慢性传染性肺病,是结核病中最常见的一种。尽管全球范围的结核病防治工作已经开展多年,但全球每年仍有大量的结核病新发病例和死亡病例,而我国作为全球第二位的结核病高负担国,结核病已经严重危害到我国人群健康,成为严峻的公共卫生问题。结核菌感染人体大多数多为隐性感染,是否发病取决于机体的免疫状态,IL-23在天然免疫和适应性免疫中扮演了重要的角色,参与众多与结核病发病相关的免疫反应,IL-23R的缺失和异常可直接影响到机体对结核菌的免疫应答,而遗传因素与机体的免疫状态密不可分。近年来IL-23R基因多态性与免疫相关疾病的关联已经被大量报道,证明了IL-23R基因异常可直接影响到机体的免疫状态从而导致发病,成为重要的致病因素。然而在结核病中,IL-23R基因多态性的研究却很少,仅在突尼斯人和中国维族人中有报道,SNPs在不同人群中分布差异较大,在汉族人群中开展IL-23R基因多态性与结核病的关联研究,对于掌握IL-23R在汉族人群中的分布状况,保护易感人群和全面了解结核病发病的遗传学机制,具有重要的意义。目的:探索白介素23受体(IL-23R)基因多态性在汉族人群中的分布,以及与肺结核发病之间的关联。方法:选取2014年3月至2015年12月在首都医科大学附属北京胸科医院所收治的肺结核住院患者作为病例组,共243例;选取北京市昌平区结核病防治所于2014年5-10月进行结核病体检的健康者作为对照组,共226名。HapMap数据库筛信息通过Haploview软件并结合文献检索选出9个IL-23R基因单核苷酸多态性(single nucleotide polymorphism,SNP)位点(rs3762318、rs11209026、rs10889657、rs10889677、rs6682925、rs1004819、rs11465804、rs2201841、rs7514847)作为待测位点,利用高温连接酶检测技术对待测位点进行检测并做基因分型,比较病例组和对照组等位基因及基因型频率,分析找出连锁不平衡和易感单倍型,从而发现该基因多态性与肺结核易感性之间的关系。结果:经过比较分析,病例组和对照组在年龄,性别,婚姻状况,文化程度上差异均无统计学意义P0.05;IL-23R多态性位点rs6682925最小等位基因C在病例组中频率为44.0%(213/484),高于对照组中的37.4%(169/452),差异有统计学意义[χ2=4.24,P=0.040;OR(95%CI)值:1.21(1.01-1.71)];基因型TT在病例组频率为30.1%(73/242),低于对照组的38.9%(88/226),差异有统计学意义[χ2=3.99,P=0.040;OR(95%CI)值:0.89(0.46-1.57)]。rs3762318等位基因C频率在病例组中为16.0%(78/486),高于对照组的10.2%(46/450),差异有统计学意义[χ2=7.04,P0.01;OR(95%CI)值:1.68(1.13-2.49)];基因型CC在病例组中频率为3.3%(8/243),高于对照组的0.4%(1/225),差异有统计学意义[χ2=5.02,P=0.040;OR(95%CI)值:7.58(0.92-60.20)];基因型TT频率在病例组中为71.5%(173/243),低于对照组的80.0%(180/225),差异有统计学意义[χ2=4.89,P=0.030;OR(95%CI)值:0.84(0.39-0.95)]。连锁分析和单倍型分析中发现由9个目标SNP位点构建的单倍型C T C A C T C T G在病例组中期望频率为5.1%,在对照组中为2.2%,差异有统计学意义[χ2=5.65,P=0.02;OR(95%CI)值:2.44(1.14-5.19)];构建单倍型域Block(rs3762318,rs10889657,rs6682925),发现单体型T T T在病例组和对照组中期望频率为55.7%和61.3%,两者差异有统计学意义[χ2=4.38,P=0.036;OR(95%CI)值:0.75(0.58-0.98)]。结论:rs6682925和rs3762318两个多态性位点的突变在汉族人群中有较高的频率,且和肺结核发病相关,单倍型C T C A C T C T G是肺结核发病的危险因素,构建单倍型域发现单倍型T T T为肺结核发病的保护因素。
[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 濮荤姸鍐，

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