Matrix metalloproteinase-9 promoter polymorphism associated with upper lung dominant emphysema
Matrix metalloproteinase-9 promoter polymorphism associated with upper lung dominant emphysema
复制标题
DOI：
10.1164/rccm.200506-953oc
复制
发表时间：
2005-12-01
影响因子：
24.7
通讯作者：
Mishima, M
中科院分区：
文献类型：
--
作者：
Ito, I;Nagai, S;Mishima, M
基本原理：基质金属蛋白酶9（MMP-9）对结缔组织蛋白具有蛋白水解活性，在慢性阻塞性肺疾病（COPD）的发生发展中起重要作用。MMP-9（C-1562 T）的功能多态性被认为是COPD易感性的候选基因之一。目的：确定MMP-9（C-1562 T）是否与日本人群中COPID的发生有关，以及是否与高分辨率计算机断层扫描（HRCT）参数评估的肺气肿的发生有关。采用限制性片段长度多态性方法检测84例COPD患者和85例健康吸烟者（对照组）的MMP-9（C-1562 T）基因型。我们使用自动分析的HRCT参数，如低密度区百分比（LAA%）和平均CT值密度，研究基因型之间的关系（Hounsfield单位;平均CTv）。测量和主要结果：MMP-9基因C-1562 T多态性在COPD组和对照组间无差异。在HRCT研究中，与无T等位基因（C/C）的患者相比，具有T等位基因（C/T或T/T）的COPD患者显示上肺的LAA%较大（差异的95%置信区间，0.5-18.7; p = 0.04），平均CTv较小（置信区间，-34.3至-1.0; p = 0.04）。然而，肺功能检查显示两组患者之间无差异。结论：MMP-9（C-1562 T）基因多态性与COPD患者上肺显性肺气肿的发生有关。
Rationale: Matrix metalloproteinase 9 (MMP-9) has proteolytic activity against connective tissue proteins and appears to play an important role in the development of chronic obstructive pulmonary disease (COPD). The functional polymorphism of MMP-9 (C-1562T) is considered as one of the candidate genes in the susceptibility to COPD.Objectives:To determine if MMP-9 (C-1562T) is related to the development of COPID in the Japanese population and whether it is associated with development of pulmonary emphysema assessed by high-resolution computed tomographic (HRCT) parameters.Methods: MMP-9 (C-1562T) genotypes of 84 patients with COPD and 85 healthy smokers (control subjects) were determined by the restriction fragment length polymorphism method. We investigated the relationship between the genotypes using automatically analyzed HRCT parameters, such as percentage of low attenuation area (LAA%) and average computed tomography (CT) value density (Hounsfield units; mean CTv) in upper, middle, and lower lung fields in all patients with COPD.Measurements and Main Results: There was no difference in polymorphism of MMP-9 (C-1562T) between patients with COPD and control subjects. In the HRCT study, patients with COPD with a T allele (C/T or T/T) showed larger LAA% (95% confidence interval of difference, 0.5-18.7; p = 0.04), and smaller mean CTv (confidence interval, -34.3 to -1.0; p = 0.04) in the upper lung compared with patients without T alleles (C/C). However, pulmonary function tests showed no difference between the two patient groups. Patients with a T allele showed a decrease in LAA% and an increase in mean CTv from upper to lower lung fields (p = 0.006 and p = 0.002, respectively).Conclusions: Polymorphism of MMP-9 (C-1562T) was associated with upper lung dominant emphysema in patients with COPD.