Wang Xinyan, Li Wan, Huang Kun, Kang Xiaowen, Li Zhaoguo, Yang Chengcheng, Wu Xiaomei, Chen Lina
Department of Respiratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
BMC Pulm Med. 2014 Nov 4;14:173. doi: 10.1186/1471-2466-14-173.
Genetic factors play a role in the development and severity of chronic obstructive pulmonary disease (COPD). The pathogenesis of COPD is a multifactorial process including an inflammatory cell profile. Recent studies revealed that single nucleotide polymorphisms (SNPs) within ADAM33 increased the susceptibility to COPD through changing the airway inflammatory process and lung function.
In this paper, we investigated associations of four polymorphisms (T1, T2, S2 and Q-1) of ADAM33 as well as their haplotypes with pulmonary function and airway inflammatory process in an East Asian population of patients with COPD.
We found that T1, T2 and Q-1 were significantly associated with the changes of pulmonary function and components of cells in sputum of COPD, and T1 and Q-1 were significantly associated with cytokines and mediators of inflammation in airway of COPD in recessive models. 10 haplotypes were significantly associated with transfer factor of the lung for carbon monoxide in the disease state, 4 haplotypes were significantly associated with forced expiratory volume in one second, and other haplotypes were associated with airway inflammation.
We confirmed for the first time that ADAM33 was involved in the pathogenesis of COPD by affecting airway inflammation and immune response in an East Asian population. Our results made the genetic background of COPD, a common and disabling disease, more apparent, which would supply genetic support for the study of the mechanism, classification and treatment for this disease.
遗传因素在慢性阻塞性肺疾病（COPD）的发生发展及严重程度中起作用。COPD的发病机制是一个多因素过程，包括炎症细胞谱。最近的研究表明，ADAM33基因内的单核苷酸多态性（SNP）通过改变气道炎症过程和肺功能增加了患COPD的易感性。
在本文中，我们研究了ADAM33基因的四种多态性（T1、T2、S2和Q-1）及其单倍型与东亚COPD患者群体的肺功能和气道炎症过程之间的关联。
我们发现，T1、T2和Q-1与COPD患者的肺功能变化及痰液中的细胞成分显著相关，在隐性模型中，T1和Q-1与COPD气道中的炎症细胞因子和介质显著相关。10种单倍型与疾病状态下的肺一氧化碳转运因子显著相关，4种单倍型与一秒用力呼气量显著相关，其他单倍型与气道炎症相关。
我们首次证实，在东亚人群中，ADAM33通过影响气道炎症和免疫反应参与了COPD的发病机制。我们的研究结果使常见致残性疾病COPD的遗传背景更加清晰，这将为该疾病的机制、分类和治疗研究提供遗传支持。
