Analysis of Genetic Contribution in the Development of Chronic Obstructive Pulmonary Disease

慢性阻塞性肺疾病发展中的遗传因素分析

基本信息

批准号：
17590783
负责人：
HANAOKA Masayuki
金额：
$ 1.6万
依托单位：
SHINSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

1) TRANSFORMING GROWTH FACTOR BETA 1 GENE POLYMORPHISMS IN EMPHYSEMA PHENOTYPE IN COPDGenetic factors are likely to influence the development of COPD, and the transforming growth factor beta 1 gene (TGFB1) is one of the most probable candidate genes which could be associated with emphysema. Eight single nucleic polymorphisms (SNPs) in the TGFB1 (rs2241712, rs1987072, rs1800469, rs1982073, rs2241716, rs4803455, rs6957 and rs2241718) were genotyped by allelic discrimination assay in seventy COPD patients with emphysema phenotype and ninety nine control smokers among Japanese. The emphysema phenotype was identified on high-resolution computed tomography image by Goddard's method. Two SNPs in the 3' genomic region (rs6957 and rs2241718) were associated with emphysema phenotype after adjusting age, sex, and smoking history. Another two SNPs (rs1800496 and rs1982073) showed significant association with the percentage of forced expiratory volume in 1 second after administration of bronchodila … More tor in the patients with emphysema phenotype. Additionally, the frequency of one haplotype was significantly different between emphysema group and control group. The current study focusing on emphysema phenotype reveals that several SNPs in the TGFB1 are associated with emphysema phenotype in COPD among Japanese population.2) PULMONARY HEMODYNAMICS IN PATIENTS WITH SEVERE COPDTo examine the pulmonary hemodynamics in severe COPD (%FEV_1 < 50%), right heart catheterization was performed in six patients with COPD during rest, exercise and exacerbation. The pulmonary artery pressure (Ppa), as pulmonary artery wedge pressure and cardiac index were significantly increased during bicycle ergometer exercise. In contrast, pulmonary vascular resistance significantly increased during exacerbation accompanied by a slightly increased Ppa. Supplemental oxygen resulted in significant decrease in Ppa during exercise and exacerbation. The principal pathophysiology of the pulmonary circulation between exercise and exacerbation might differ in severe COPD. Supplemental oxygen is beneficial in these situations as reflected by improved pathological pulmonary hypertension. Less

1) COPD肺气肿表型中的转化生长因子β1基因多态性遗传因素可能影响COPD的发展，转化生长因子β1基因(TGFB1)是最有可能与肺气肿相关的候选基因之一。 TGFB1 中的八个单核酸多态性 (SNP)（rs2241712、 rs1987072、rs1800469、rs1982073、rs2241716、rs4803455、rs6957 和 rs2241718）通过等位基因区分分析对日本 70 名患有肺气肿表型的 COPD 患者和 99 名对照吸烟者进行基因分型，并通过高分辨率计算机断层扫描图像识别了肺气肿表型。通过Goddard 方法显示，在调整年龄、性别和吸烟史后，3' 基因组区域中的两个 SNP（rs6957 和 rs2241718）与肺气肿表型相关，另外两个 SNP（rs1800496 和 rs1982073）显示与用力呼气量百分比显着相关。肺气肿表型患者服用支气管扩张剂后 1 秒。肺气肿组和对照组之间一种单倍型的频率存在显着差异。目前针对肺气肿表型的研究表明，TGFB1 中的几个 SNP 与日本人群中 COPD 的肺气肿表型相关。2) 重度 COPD 患者的肺血流动力学检查。重度COPD（%FEV_1 < 50%）的肺血流动力学，对6名COPD患者进行了右心导管检查休息、运动和恶化期间，肺动脉压（Ppa）显着增加，因为肺动脉楔压和心脏指数在自行车测力计运动期间显着增加，相反，在恶化期间肺血管阻力显着增加，并伴随着补充氧气的轻微增加。运动和急性加重期间 Ppa 显着下降运动和急性加重期间肺循环的主要病理生理学可能有所不同，补充氧气在这些情况下是有益的，如改善所示。病理性肺动脉高压较少。