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

1)转化生长因子β 1基因多态性与COPD肺气肿的关系遗传因素可能影响COPD的发生发展，转化生长因子β 1基因（transforminggrowthfactorbeta1，TGFB1）是最可能与肺气肿相关的候选基因之一。通过等位基因鉴别分析，对70例COPD肺气肿患者和99例对照吸烟者的TGFB1基因的8个单核苷酸多态性（SNP）（rs2241712、rs1987072、rs1800469、rs1982073、rs2241716、rs4803455、rs6957和rs2241718）进行基因分型。采用戈达德方法在高分辨率CT图像上识别肺气肿表型。在调整年龄、性别和吸烟史后，3'基因组区域的两个SNP（rs6957和rs2241718）与肺气肿表型相关。另外两个SNPs（rs1800496和rs1982073）与支气管扩张剂给药后1秒用力呼气容积百分比显著相关 ...更多信息 在肺气肿表型患者中，此外，单倍型的频率在肺气肿组和对照组之间存在显著差异。目前的研究集中在肺气肿表型上，揭示了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为了检查重度COPD（%FEV_1 < 50%）的肺血流动力学，对6名COPD患者在休息、运动和加重期间进行右心导管插入术。踏车运动时肺动脉压（Ppa）、肺动脉楔压和心脏指数均显著升高。相反，肺血管阻力在急性加重期间显著增加，伴有Ppa略微增加。补充氧气导致运动和急性加重期间Ppa显著降低。在重度COPD患者中，运动和急性加重之间的肺循环的主要病理生理学可能不同。在这些情况下，补充氧气是有益的，这反映在病理性肺动脉高压的改善上。少

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