發(fā)布時間：2018-07-09 21:15

  本文選題：胸腺基質淋巴細胞生成素 + 單核苷酸多態(tài)��； 參考：《山東大學》2012年碩士論文

【摘要】：研究背景： 支氣管哮喘是由多種炎性細胞(如嗜酸性粒細胞、肥大細胞、T淋巴細胞、中性粒細胞等)、氣道結構細胞(如平滑肌細胞、氣道上皮細胞等)和細胞組分參與的氣道的一種慢性變態(tài)反應性炎癥性疾病,是常見的慢性呼吸系統(tǒng)疾病之一,全球有3億支氣管哮喘患者,我國支氣管哮喘患者已超過2000萬。許多患者的病程長達十幾年至幾十年,有些已影響其勞動能力及生活質量,成為患者家庭和全社會沉重的負擔。因此,從發(fā)病機制入手尋找治療治愈支氣管哮喘的方法已成為亟待解決的社會問題,然而支氣管哮喘的發(fā)病機制十分復雜,主要包括遺傳因素和環(huán)境因素兩個方面。多數(shù)家系聚集、孿生及大的遺傳隊列研究均證實,支氣管哮喘存在著遺傳易感性。近些年來實驗研究證實發(fā)現(xiàn),一種IL-7樣細胞因子,也就是胸腺基質淋巴細胞生成素(TSLP)在支氣管哮喘發(fā)生、發(fā)展中起重要作用。日本學者Michishige等研究發(fā)現(xiàn)TSLP的3個單核苷酸多態(tài)位點(SNP)(rs3806933、rs2289276和rs2289278)中的rs3806933和rs2289276與兒童及成人支氣管哮喘均相關,位點rs2289278與支氣管哮喘的肺功能受損相關。 研究目的： 檢測中國漢族人群胸腺基質淋巴細胞生成素(thymic stromal lymphopoietin,TSLP)基因啟動子區(qū)域的單核苷酸多態(tài)(single-nucleotide polymorphism, SNP)位點Rs2289276及Rs2289278的多態(tài)性,利用基于群體的病例對照關聯(lián)分析探討TSLP基因啟動子區(qū)域單核苷酸多態(tài)與中國漢族哮喘相關性及與肺功能相關性研究。 研究方法： 收集531例支氣管哮喘患者及年齡、性別匹配的正常對照540例,根據(jù)知情同意原則采集2m1外周血,提取外周血DNA,進行合酶鏈反應,采用聚合酶鏈反應一限制性片斷長度多態(tài)性(polymerase chain reaction and restriction fragment length polymorphism,PCR-RFLP)方法檢測TSLP基因啟動子區(qū)域SNP位點Rs2289276及Rs2289278的基因型,計算基因型頻率及等位基因頻率,進行x2檢驗,探討兩SNP位點與哮喘相關性及等位基因與肺功能相關性。 研究結果： Rs2289276位點CC/CT/TT基因型頻率在病例組中為0.4706/0.4392/0.0902,在對照組中為0.5604/0.3800/0.0595；Rs2289278位點CC/CT/TT基因型頻率在病例組中為0.6502/0.2966/0.0532,在對照組中為0.5795/0.3428/0.0777,兩位點的基因型、等位基因分布以及單倍體型分布在哮喘組與對照組之間均有統(tǒng)計學差異(P≤0.05)。Rs2289278位點C等位基因與FEV,/FVC的下降相關(P≤O.05)。 研究結論： 1.中國漢族人群TSLP基因啟動子區(qū)域單核苷酸多態(tài)Rs2289276和Rs2289278與支氣管哮喘易感性相關。 2.Rs2289278位點C等位基因與FEV1/FVC的下降相關。 3. TSLP基因可能為支氣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，

本文編號：2110679