ADAM33基因单核苷酸多态性及单体型与慢性阻塞性肺疾病的关联性研究

发布时间：2018-05-11 14:01

本文选题：慢性阻塞性肺疾病 + 解整合素金属蛋白酶类　；参考：《山西医科大学》2012年硕士论文

【摘要】：[目的] 探讨ADAM (a disintegrin and metalloprotease,解整合素—金属蛋白酶)33基因单核苷酸多态性及单体型与中国华北地区汉族人群慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)的关联性,确定在中国华北地区汉族人群中ADAM33基因是否为COPD的易感基因,为今后COPD发病机制的阐述提供新的理论依据。 [方法] 1根据中华医学会呼吸病学会分会制定的COPD诊治指南(2007年修订版)的诊断标准,选取2010年09月—2011年06月太原市中心医院呼吸内科门诊或住院确诊的COPD患者90例为病例组,同期该院健康体检者90例为对照组。所有受试对象均为中国华北地区汉族人,并经过详细的询问病史、体格检查、肺功能测定及胸部X线片检查排除支气管哮喘、支气管扩张症、肺结核、肺间质纤维化、弥漫性泛细支气管炎、支气管肺癌等呼吸系统疾病。 2抽取所有受试者静脉血2m1,提取基因组DNA,利用PCR技术扩增ADAM33基因上包含S1,S2位点的片段,采用DNA直接测序的方法对该片段进行基因分型,测算基因型频率及等位基因频率,并利用SHEsis软件构建S1、S2位点的单体型,计算单体型频率。 [结果] (1)病例组和对照组中S1位点基因型及等位基因频率分布比较差异无统计学意义(P0.05),而S2位点基因型及等位基因频率分布比较差异有统计学意义(P0.05)。 (2) Logistic回归分析表明：ADAM33基因S1位点不同基因型COPD发生的相对危险度比较差异没有统计学意义(P0.05)；而S2位点不同基因型COPD发生的相对危险度比较差异有统计学意义(P0.05),其中G/G+C/G基因型的OR值为2.364(95%CI1.251-4.466)。 (3) COPD病例组S2位点基因型与肺功能相关临床指标的关系显示：3种基因型FEV1%预测值比较差异没有统计学意义而FEV1/FVC比较差异有统计学意义,其中突变纯合子G/G基因型与野生纯合子C/C、杂合子C/G基因型相比FEV1/FVC下降更明显。 (4) SHEsis在线软件对S1、S2位点进行单体型分析结果显示：单体型CG在COPD组和对照组中比较差异有统计学意义(P0.05) [结论] ADAM33基因单核苷酸多态性及单体型与中国华北地区汉族人群COPD的易感性有关联,但与疾病的严重程度无关。
[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.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R563.9

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