TSLP基因启动子区域两单核苷酸多态性与中国汉族人群哮喘的相关性研究

发布时间：2018-07-09 21:15

  本文选题：胸腺基质淋巴细胞生成素 + 单核苷酸多态　； 参考：《山东大学》2012年硕士论文

【摘要】：研究背景： 支气管哮喘是由多种炎性细胞(如嗜酸性粒细胞、肥大细胞、T淋巴细胞、中性粒细胞等)、气道结构细胞(如平滑肌细胞、气道上皮细胞等)和细胞组分参与的气道的一种慢性变态反应性炎症性疾病,是常见的慢性呼吸系统疾病之一,全球有3亿支气管哮喘患者,我国支气管哮喘患者已超过2000万。许多患者的病程长达十几年至几十年,有些已影响其劳动能力及生活质量,成为患者家庭和全社会沉重的负担。因此,从发病机制入手寻找治疗治愈支气管哮喘的方法已成为亟待解决的社会问题,然而支气管哮喘的发病机制十分复杂,主要包括遗传因素和环境因素两个方面。多数家系聚集、孪生及大的遗传队列研究均证实,支气管哮喘存在着遗传易感性。近些年来实验研究证实发现,一种IL-7样细胞因子,也就是胸腺基质淋巴细胞生成素(TSLP)在支气管哮喘发生、发展中起重要作用。日本学者Michishige等研究发现TSLP的3个单核苷酸多态位点(SNP)(rs3806933、rs2289276和rs2289278)中的rs3806933和rs2289276与儿童及成人支气管哮喘均相关,位点rs2289278与支气管哮喘的肺功能受损相关。 研究目的： 检测中国汉族人群胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)基因启动子区域的单核苷酸多态(single-nucleotide polymorphism, SNP)位点Rs2289276及Rs2289278的多态性,利用基于群体的病例对照关联分析探讨TSLP基因启动子区域单核苷酸多态与中国汉族哮喘相关性及与肺功能相关性研究。 研究方法： 收集531例支气管哮喘患者及年龄、性别匹配的正常对照540例,根据知情同意原则采集2m1外周血,提取外周血DNA,进行合酶链反应,采用聚合酶链反应一限制性片断长度多态性(polymerase chain reaction and restriction fragment length polymorphism,PCR-RFLP)方法检测TSLP基因启动子区域SNP位点Rs2289276及Rs2289278的基因型,计算基因型频率及等位基因频率,进行x2检验,探讨两SNP位点与哮喘相关性及等位基因与肺功能相关性。 研究结果： Rs2289276位点CC/CT/TT基因型频率在病例组中为0.4706/0.4392/0.0902,在对照组中为0.5604/0.3800/0.0595；Rs2289278位点CC/CT/TT基因型频率在病例组中为0.6502/0.2966/0.0532,在对照组中为0.5795/0.3428/0.0777,两位点的基因型、等位基因分布以及单倍体型分布在哮喘组与对照组之间均有统计学差异(P≤0.05)。Rs2289278位点C等位基因与FEV,/FVC的下降相关(P≤O.05)。 研究结论： 1.中国汉族人群TSLP基因启动子区域单核苷酸多态Rs2289276和Rs2289278与支气管哮喘易感性相关。 2.Rs2289278位点C等位基因与FEV1/FVC的下降相关。 3. TSLP基因可能为支气管哮喘的易感基因之一。
[Abstract]:Background: bronchial asthma is composed of a variety of inflammatory cells (such as eosinophils, mast cells, T lymphocytes, neutrophils, etc.), airway structural cells (such as smooth muscle cells, etc.). A chronic allergic inflammatory disease of the airway in which airway epithelial cells and cell components participate is one of the common chronic respiratory diseases. There are 300 million bronchial asthma patients in the world and more than 20 million in China. The course of disease of many patients lasts for more than ten years to several decades, some of them have affected their labor ability and quality of life, and become a heavy burden on patients' families and the whole society. Therefore, it has become an urgent social problem to find a cure for bronchial asthma from pathogenesis. However, the pathogenesis of bronchial asthma is very complicated, including genetic factors and environmental factors. Clustering, twinning and large genetic cohort studies in most families confirmed the genetic susceptibility to bronchial asthma. In recent years, experimental studies have confirmed that a kind of IL-7-like cytokine, thymic stromal lymphopoietin (TSLP), plays an important role in the occurrence and development of bronchial asthma. Michishige, a Japanese scholar, found that rs3806933 and rs2289276 in three single nucleotide polymorphisms (SNPs) (rs3806933, rs2289276 and rs2289278) of TSLP were associated with bronchial asthma in children and adults, and that rs2289278 loci were associated with lung dysfunction in asthma. Objective: to detect the polymorphisms of single-nucleotide polymorphisms (Rs2289276 and Rs2289278) in the promoter region of thymus stromal lymphopoietin (thymic stromal lymphopoietine) gene in Chinese Han population. The association of single nucleotide polymorphism in promoter region of TSLP gene with asthma and pulmonary function in Chinese Han nationality was studied by case-control analysis based on population. Methods: 531 patients with bronchial asthma and 540 normal controls matched by age and sex were collected. 2m1 peripheral blood was collected according to informed consent principle, and DNA was extracted from peripheral blood for polymerase chain reaction (PCR). The genotypes of SNP sites Rs2289276 and Rs2289278 in the promoter region of TSLP were detected by polymerase chain reaction-restriction fragment length polymorphism (polymerase chain reaction and restriction fragment length) PCR-RFLP. The genotype frequency and allele frequency were calculated and x2 test was performed. To investigate the correlation between two SNP loci and asthma and between alleles and pulmonary function. The results showed that the frequency of CCR / CTP TT genotype at Rs2289276 was 0.4706 / 0.4392- 0.0902 in the case group, 0.5604 / 0.3800 / 0.0595rs2289278 in the control group, 0.6502r / 0.2966 / 0.0532in the case group and 0.5795r0.3428280.07777 in the control group. The allele distribution and haploid distribution were significantly different between asthma group and control group (P 鈮，

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