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

1)COPD肺气肿表型中转化生长因子β1基因多态性遗传因素可能影响COPD的发生发展，转化生长因子β1基因(TGFB1)是最可能与肺气肿相关的候选基因之一。采用等位基因鉴别法对70例COPD肺气肿表型患者和99例对照吸烟者的TGFB1基因8个单核苷酸多态性(rs2241712、rs1987072、rs1800469、rs1982073、rs2241716、rs4803455、rs6957和rs2241718)进行了基因分型。用Goddard方法在高分辨率CT图像上识别肺气肿表型。在调整了年龄、性别和吸烟史后，3‘端基因组区域的两个SNP(rs6957和rs2241718)与肺气肿表型相关。另外两个SNPs(rs1800496和rs1982073)与服用…后1秒内用力呼气量的百分比显著相关肺气肿表型的患者更多。单倍型频率在肺气肿组和对照组之间有显著差异。目前对肺气肿表型的研究揭示了TGFB1中的几个SNPs与日本人群中COPD的肺气肿表型有关。2)重度COPD患者的肺血流动力学为了检测重度COPD(%FEV_1&lt；50%)患者的肺血流动力学，对6名COPD患者在静息、运动和病情加重时进行了右心导管术。在自行车运动中，肺动脉压(PPA)、肺动脉楔压和心脏指数均显著升高。相反，在急性加重期，肺血管阻力显著增加，并伴有轻微的PPA升高。补充氧气可显著降低运动期间和病情加重时的PPA。重度COPD患者运动和加重时肺循环的主要病理生理学改变可能不同。补充氧气在这些情况下是有益的，这反映在病理性肺动脉高压的改善上。较少

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