The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function
The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function
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DOI：
10.1093/hmg/11.5.569
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发表时间：
2002-03-01
影响因子：
3.5
通讯作者：
Sandford, AJ
中科院分区：
文献类型：
--
作者：
Joos, L;He, JQ;Sandford, AJ
基质金属蛋白酶（MMP）包括在组织重塑中起重要作用的至少20种蛋白水解酶的家族。MMP 1（间质胶原酶）、MMP 9（明胶酶B）和MMP 12（巨噬细胞弹性蛋白酶）被认为在肺气肿的发展中是重要的。已经鉴定了许多天然存在的人MMP基因启动子多态性，并发现其改变转录活性。此外，我们检测到一种新的多态性在MMP 12编码区（Asn 357 Ser）。本研究旨在探讨MMP基因多态性在慢性阻塞性肺疾病发病中的作用。我们从国家心肺和血液研究所肺健康研究中选择了590名持续吸烟者，确定了这些多态性的患病率，这些吸烟者具有最快的（n = 284）和最慢的（n = 306）5年肺功能下降率。在这五种多态性中，只有G-1607 GG与肺功能下降率相关。-1607GG等位基因与快速下降呈负相关（P = 0.02）。然而，由MMP 1G-1607 GG和MMP 12 Asn 357 Ser多态性等位基因组成的单倍型与肺功能下降率相关（P = 0.0007）。这些数据表明，MMP 1和MMP 12基因的多态性，而不是MMP 9，是吸烟相关肺损伤的致病因素或与致病多态性连锁不平衡。
The matrix metalloproteinases (MMPs) comprise a family of at least 20 proteolytic enzymes that play an essential role in tissue remodeling. MMP1 (interstitial collagenase), MMP9 (gelatinase B) and MMP12 (macrophage elastase) are thought to be important in the development of emphysema. A number of naturally occurring polymorphisms of human MMP gene promoters have been identified and found to alter transcriptional activity. Additionally, we detected a novel polymorphism in the MMP12 coding region (Asn357Ser). The aim of this study was to investigate the role of MMP polymorphisms in the development of chronic obstructive lung disease. We determined the prevalence of these polymorphisms in 590 continuing smokers chosen from the National Heart Lung and Blood Institute, Lung Health Study for having the fastest (n = 284) and slowest (n = 306) 5 year rate of decline of lung function. Of the five polymorphisms, only G-1607GG was associated with a rate of decline in lung function. The -1607GG allele was negatively associated with a fast rate of decline (P = 0.02). However, haplotypes consisting of alleles from the MMP1 G-1607GG and MMP12 Asn357Ser polymorphisms were associated with rate of decline of lung function (P = 0.0007). These data suggest that polymorphisms in the MMP1 and MMP12 genes, but not MMP9, are either causative factors in smoking-related lung injury or are in linkage disequilibrium with causative polymorphisms.