本文選題：慢性阻塞性肺疾病　切入點(diǎn)：SERPINE2　出處：《山東大學(xué)》2009年碩士論文

【摘要】： 目的時(shí)至今日,慢性阻塞性肺疾病(COPD)已經(jīng)發(fā)展成為嚴(yán)重危害廣大人民群眾,尤其是中老人身體健康的重要疾病之一。國內(nèi)外眾多研究表明,COPD是一種受多種基因和環(huán)境因素影響的復(fù)雜的疾病。除環(huán)境因素外,吸煙是公認(rèn)的引起COPD的重要危險(xiǎn)因素,但只有少數(shù)吸煙者患有COPD。通過對于肺功能的測試顯示,在波士頓早發(fā)性COPD家族研究中,Genomewide連鎖分析表明2號(hào)染色體長臂與疾病呈強(qiáng)相關(guān)性。用表達(dá)譜分析小鼠和人的肺組織,DeMeo以及他的同事發(fā)現(xiàn)位于2q上的SERPINE2(絲氨酸蛋白酶抑制劑-2或纖溶酶原激活物抑制物1)是與COPD相關(guān)的易感基因。我們的目的是探討血清中SERPINE2基因多態(tài)性與慢性阻塞性肺疾病(COPD)表型的相關(guān)性,從而進(jìn)一步的明確COPD的發(fā)病機(jī)制。 材料和方法采用病例-對照研究的方法,收集100例中國漢族患者。選取了2007年10月至2008年6月間山東大學(xué)齊魯醫(yī)院門診和住院漢族病人100例為實(shí)驗(yàn)組,符合2007年慢性阻塞性肺疾病診治指南的診斷標(biāo)準(zhǔn)。病人吸入沙丁胺醇200μg 15min后,一秒鐘用力呼氣容積占預(yù)計(jì)值百分比(FEV1占預(yù)計(jì)值%)均＜70%。選取同一時(shí)間本院健康體檢者100例為對照組,胸部影像學(xué)正常,肺功能FEV1/FVC＞70%,FEV1占預(yù)計(jì)值%＞80%。提取基因組DNA,使用Primer Express2.0軟件設(shè)計(jì)普通TaqMan探針和引物,通過等位基因特異性的探針檢測兩組人群血清中單核苷酸多態(tài)性(single nucleotide polymorphisms,SNPs),判定單個(gè)樣本的基因型。 結(jié)果rs6734100位點(diǎn)的突變與COPD不存在相關(guān)性。在病例組和正常組的突變頻率分別為2.5%、0.0%,經(jīng)χ2檢驗(yàn)兩組無統(tǒng)計(jì)學(xué)意義(P＞0.05)。按照肺功能將病例組分為Ⅰ、Ⅱ、Ⅲ、Ⅳ級(分級標(biāo)準(zhǔn)見2007年慢性阻塞性肺疾病診治指南),進(jìn)行χ2檢驗(yàn)4組無統(tǒng)計(jì)學(xué)差異(P＞0.05)。吸煙指數(shù)、SERPINE2 rs6734100多態(tài)性對COPD發(fā)生交互作用的相關(guān)分析,吸煙指數(shù)與COPD的相關(guān)系數(shù)γ為0.208(P=0.112),SERPINE2rs6734100多態(tài)性與COPD的相關(guān)系數(shù)γ為0.056(P=0.787)。兩者P值均＞0.05,無統(tǒng)計(jì)學(xué)意義。 結(jié)論SERPINE2不是漢族人群COPD的易感基因。國外文獻(xiàn)通過對小鼠和人類2q區(qū)域基因信息的連鎖分析,已經(jīng)證明SERPINE2基因的變異位點(diǎn)與COPD相關(guān)。目前國內(nèi)尚未有關(guān)于SERPINE2基因多態(tài)性與COPD發(fā)病相關(guān)性的研究,本實(shí)驗(yàn)通過檢測國人SERPINE2基因rs6734100位點(diǎn)的多態(tài)性與國外相似實(shí)驗(yàn)進(jìn)行比較,顯示SERPINE2 rs6734100位點(diǎn)的突變與COPD并無明顯相關(guān)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，

本文編號(hào)：1727938