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  本文選題：慢性阻塞性肺疾病 + 解整合素金屬蛋白酶類��； 參考：《山西醫(yī)科大學(xué)》2012年碩士論文

【摘要】：[目的] 探討ADAM (a disintegrin and metalloprotease,解整合素—金屬蛋白酶)33基因單核苷酸多態(tài)性及單體型與中國華北地區(qū)漢族人群慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)的關(guān)聯(lián)性,確定在中國華北地區(qū)漢族人群中ADAM33基因是否為COPD的易感基因,為今后COPD發(fā)病機(jī)制的闡述提供新的理論依據(jù)。 [方法] 1根據(jù)中華醫(yī)學(xué)會呼吸病學(xué)會分會制定的COPD診治指南(2007年修訂版)的診斷標(biāo)準(zhǔn),選取2010年09月—2011年06月太原市中心醫(yī)院呼吸內(nèi)科門診或住院確診的COPD患者90例為病例組,同期該院健康體檢者90例為對照組。所有受試對象均為中國華北地區(qū)漢族人,并經(jīng)過詳細(xì)的詢問病史、體格檢查、肺功能測定及胸部X線片檢查排除支氣管哮喘、支氣管擴(kuò)張癥、肺結(jié)核、肺間質(zhì)纖維化、彌漫性泛細(xì)支氣管炎、支氣管肺癌等呼吸系統(tǒng)疾病。 2抽取所有受試者靜脈血2m1,提取基因組DNA,利用PCR技術(shù)擴(kuò)增ADAM33基因上包含S1,S2位點的片段,采用DNA直接測序的方法對該片段進(jìn)行基因分型,測算基因型頻率及等位基因頻率,并利用SHEsis軟件構(gòu)建S1、S2位點的單體型,計算單體型頻率。 [結(jié)果] (1)病例組和對照組中S1位點基因型及等位基因頻率分布比較差異無統(tǒng)計學(xué)意義(P0.05),而S2位點基因型及等位基因頻率分布比較差異有統(tǒng)計學(xué)意義(P0.05)。 (2) Logistic回歸分析表明：ADAM33基因S1位點不同基因型COPD發(fā)生的相對危險度比較差異沒有統(tǒng)計學(xué)意義(P0.05)；而S2位點不同基因型COPD發(fā)生的相對危險度比較差異有統(tǒng)計學(xué)意義(P0.05),其中G/G+C/G基因型的OR值為2.364(95%CI1.251-4.466)。 (3) COPD病例組S2位點基因型與肺功能相關(guān)臨床指標(biāo)的關(guān)系顯示：3種基因型FEV1%預(yù)測值比較差異沒有統(tǒng)計學(xué)意義而FEV1/FVC比較差異有統(tǒng)計學(xué)意義,其中突變純合子G/G基因型與野生純合子C/C、雜合子C/G基因型相比FEV1/FVC下降更明顯。 (4) SHEsis在線軟件對S1、S2位點進(jìn)行單體型分析結(jié)果顯示：單體型CG在COPD組和對照組中比較差異有統(tǒng)計學(xué)意義(P0.05) [結(jié)論] ADAM33基因單核苷酸多態(tài)性及單體型與中國華北地區(qū)漢族人群COPD的易感性有關(guān)聯(lián),但與疾病的嚴(yán)重程度無關(guān)。
[Abstract]:[purpose] To investigate the association of single nucleotide polymorphism (SNP) and haplotype of integrin-metalloproteinase-33 gene (SNP33) in ADAM disintegrin and metalloprotease, with chronic obstructive pulmonary disease (obstructive pulmonary disease, COPD) in Chinese Han population in North China. To determine whether the ADAM33 gene is a susceptible gene of COPD in the Han population of North China, and to provide a new theoretical basis for the elucidation of the pathogenesis of COPD in the future. [methods] 1According to the diagnostic criteria of COPD diagnosis and treatment guidelines (revised edition, 2007), 90 COPD patients diagnosed in Department of Respiratory Medicine of Taiyuan Central Hospital from September 2010 to June 2011 were selected as the case group. At the same time, 90 healthy persons in the hospital were taken as the control group. All subjects were Han nationality in North China. After detailed inquiry of history, physical examination, pulmonary function test and chest X-ray examination, bronchial asthma, bronchiectasis, pulmonary tuberculosis, pulmonary interstitial fibrosis were excluded. Diffuse panbronchiolitis, bronchial lung cancer and other respiratory diseases. 2Genomic DNA was extracted from venous blood of all the subjects, and the gene fragment containing S1FS2 site in ADAM33 gene was amplified by PCR technique. Genotyping of the fragment was carried out by DNA direct sequencing, and genotypic frequency and allele frequency were calculated. Haplotype of S _ 1 / S _ 2 locus was constructed by SHEsis software, and haplotype frequency was calculated. [results] 1) there was no significant difference in the frequency distribution of S1 locus genotype and allele between the case group and the control group, but there was a significant difference in the frequency distribution of S2 locus genotype and allele between the two groups. (2) Logistic regression analysis showed that there was no significant difference in the relative risk between different genotypes of COPD at S1 locus of the 1: ADAM33 gene, but there was a significant difference in the relative risk degree of COPD in different genotypes of S2 locus. The OR value of the G / G C / G genotype was 2.364% 95% CI 1.251-4.466%. (3) the relationship between S2 locus genotype and lung function related clinical indexes in COPD patients showed that there was no significant difference in FEV1% predictive value among the three COPD genotypes, but there was significant difference in FEV1/FVC comparison. The FEV1/FVC of the mutant homozygote G / G genotype was significantly lower than that of wild homozygote C / C and heterozygote C / G genotype. (4) haplotype analysis of S1 / S2 locus by SHEsis software showed that haplotype CG was significantly different between COPD group and control group (P0.05). [conclusion] The single nucleotide polymorphism and haplotype of ADAM33 gene were associated with the susceptibility to COPD in Han population in North China, but not with the severity of the disease.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R563.9

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本文編號：1874255