SERPINE2基因多态性与慢性阻塞性肺疾病的相关性研究

发布时间：2018-04-09 20:05

  本文选题：慢性阻塞性肺疾病　切入点：SERPINE2　出处：《山东大学》2009年硕士论文

【摘要】： 目的时至今日,慢性阻塞性肺疾病(COPD)已经发展成为严重危害广大人民群众,尤其是中老人身体健康的重要疾病之一。国内外众多研究表明,COPD是一种受多种基因和环境因素影响的复杂的疾病。除环境因素外,吸烟是公认的引起COPD的重要危险因素,但只有少数吸烟者患有COPD。通过对于肺功能的测试显示,在波士顿早发性COPD家族研究中,Genomewide连锁分析表明2号染色体长臂与疾病呈强相关性。用表达谱分析小鼠和人的肺组织,DeMeo以及他的同事发现位于2q上的SERPINE2(丝氨酸蛋白酶抑制剂-2或纤溶酶原激活物抑制物1)是与COPD相关的易感基因。我们的目的是探讨血清中SERPINE2基因多态性与慢性阻塞性肺疾病(COPD)表型的相关性,从而进一步的明确COPD的发病机制。 材料和方法采用病例-对照研究的方法,收集100例中国汉族患者。选取了2007年10月至2008年6月间山东大学齐鲁医院门诊和住院汉族病人100例为实验组,符合2007年慢性阻塞性肺疾病诊治指南的诊断标准。病人吸入沙丁胺醇200μg 15min后,一秒钟用力呼气容积占预计值百分比(FEV1占预计值%)均＜70%。选取同一时间本院健康体检者100例为对照组,胸部影像学正常,肺功能FEV1/FVC＞70%,FEV1占预计值%＞80%。提取基因组DNA,使用Primer Express2.0软件设计普通TaqMan探针和引物,通过等位基因特异性的探针检测两组人群血清中单核苷酸多态性(single nucleotide polymorphisms,SNPs),判定单个样本的基因型。 结果rs6734100位点的突变与COPD不存在相关性。在病例组和正常组的突变频率分别为2.5%、0.0%,经χ2检验两组无统计学意义(P＞0.05)。按照肺功能将病例组分为Ⅰ、Ⅱ、Ⅲ、Ⅳ级(分级标准见2007年慢性阻塞性肺疾病诊治指南),进行χ2检验4组无统计学差异(P＞0.05)。吸烟指数、SERPINE2 rs6734100多态性对COPD发生交互作用的相关分析,吸烟指数与COPD的相关系数γ为0.208(P=0.112),SERPINE2rs6734100多态性与COPD的相关系数γ为0.056(P=0.787)。两者P值均＞0.05,无统计学意义。 结论SERPINE2不是汉族人群COPD的易感基因。国外文献通过对小鼠和人类2q区域基因信息的连锁分析,已经证明SERPINE2基因的变异位点与COPD相关。目前国内尚未有关于SERPINE2基因多态性与COPD发病相关性的研究,本实验通过检测国人SERPINE2基因rs6734100位点的多态性与国外相似实验进行比较,显示SERPINE2 rs6734100位点的突变与COPD并无明显相关性。
[Abstract]:Objective to date, chronic obstructive pulmonary disease (COPD) has developed into one of the most important diseases which seriously endangers the health of the people, especially the middle and old people.Many studies at home and abroad show that COPD is a complex disease affected by many genes and environmental factors.In addition to environmental factors, smoking is recognized as an important risk factor for COPD, but only a few smokers have copd.Tests of lung function showed that there was a strong correlation between the long arm of chromosome 2 and the disease in the early onset COPD family study in Boston.Expression profile analysis of mouse and human lung tissue DeMeo and his colleagues found that SERPINE2 (serine protease inhibitor -2 or plasminogen activator inhibitor 1), located on 2Q, is a susceptible gene associated with COPD.Our aim is to investigate the association between the polymorphism of SERPINE2 gene in serum and the phenotype of chronic obstructive pulmonary disease (COPD), so as to further clarify the pathogenesis of COPD.Materials and methods 100 Chinese Han patients were collected by case-control study.From October 2007 to June 2008, 100 outpatients and inpatients of Han nationality in Qilu Hospital of Shandong University were selected as experimental groups, which were in accordance with the diagnostic criteria of 2007 guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease (COPD).After inhaling salbutamol 200 渭 g 15min, the percentage of forced expiratory volume in one second and FEV1 in predicted value were less than 70.In the same time, 100 healthy persons were selected as control group. Chest imaging was normal, FEV1/FVC > 70% FEV1 > 80%.Genomic DNAs were extracted, and general TaqMan probes and primers were designed by Primer Express2.0 software. The single nucleotide polymorphismsSNPs were detected by allele-specific probes to determine the genotypes of individual samples.Results there was no correlation between rs6734100 mutation and COPD.The mutation frequencies in the case group and the normal group were 2.5 and 0.00.There was no significant difference between the two groups by 蠂 2 test (P > 0.05).According to the pulmonary function, the patients were divided into grade 鈪，

本文编号：1727938