慢性阻塞性肺疾病易感基因的研究进展  

Genetic polymorphisms in chronic obstructive pulmonary disease

作　　者：龚益[1] 戴然然[1] 时国朝[1] 万欢英[1] 

机构地区：[1]上海交通大学附属瑞金医院呼吸科,200025

出　　处：《国际呼吸杂志》2009年第19期1173-1177,共5页International Journal of Respiration

基　　金：该项目为国家科技部十一五支撑课题（2008BA152B00）

摘　　要：慢性阻塞性肺疾病（chronico bstructive pulmonary disease，COPD）是一种气流受限为特征的疾病，目前研究表明它是一种多基因遗传病，在基因多态性的研究中有两个平衡假说引起普遍的关注；这两个平衡就是蛋白酶／抗蛋白酶平衡和氧化物／抗氧化物平衡，由于这两个平衡被破坏，导致过分的炎症反应和组织破坏。涉及这方面的基因包括：α1-抗胰蛋白酶、金属基质蛋白酶、金属蛋白酶组织抑制剂-2、VitD相关蛋白、谷胱甘肽转移酶s、微粒体环氧化物水解酶、HOX-1、肿瘤坏死因子α和白介素1等。有报道表明不同基因或同一基因的不同位点间可能存在联合作用。动物模型基因研究会帮助区分一些病理过程，如果这种研究继以定量分析可能会帮助确定将来人的易感基因。但是全基因组的相关分析意味着需要分析大量的基因数据，计算机辅助软件或医工结合可能会解决部分问题。由于存在人种差异，所以应该寻求在不同独立的人种间确定阳性结果。对这些结果进行整合可能可以更准确的确定COPD，并且对那些更可能发生COPD的亚群进行靶向治疗。Etiology of chronic obstructive pulmonary disease remains unknown but despite some inconsistencies in reports on inflammatory cells, mediators and proteases involved in the pathogenesis of chronic obstructive pulmonary disease,genetic risk factors were proposed as a cause of susceptibility to the disease. Results of many studies suggested polygenic inheritance, with the genetic component consisting of several genes of a small effect each, rather than of single major gene. We are going to review the clinical importance of alpha-1 antitrypsin, matrix metalloproteinase, Tissue inhibitor of metalloproteinases-2, Vitamin-D-binding protein, glutathione S-transferase, microsomal epoxide hydrolase, heine oxygenase-1 genes,Surfacant protein and IL-8, TNF-α polymorphisms associated with susceptibility and progression of the chronic obstructive pulmonary disease. It was reported that there are combination with different genes or different locus in the same gene. Animal model genetics may help in clarifying some aspects of pathogenesis. If this type of study were followed by quantitative trait locus analysis it may help to identify candidate genes for further study in humans. Genome-wide association analysis may now be＇performed looking for up to 500000 SNP＇s at any one time to identify regions in linkage disequilibrium （LD） with features of COPD. This approach does, however, have limitations. It means there are millions of data to analysis, but Software available from industry and academia can help to deal with that. The number of areas being investigated will raise the potential for false positive results, so confirmation of any positive results in multiple independent populations should be sought. As more genes are identified we may be able to characterize patients with COPD more accurately and target therapies to those subgroups most likely to benefit.

关 键 词：慢性阻塞性肺疾病 氧化物/抗氧化物 蛋白酶/抗蛋白酶 炎症 基因多态性 

分 类 号：R563.9[医药卫生—呼吸系统]