MMP12, Lung Function, and COPD in High-Risk Populations

A variant of MMP12, encoding a matrix metallopeptidase, is associated with increased lung function in children with asthma and in adult smokers. It is also associated with a decreased risk of chronic obstructive pulmonary disease in adult smokers. A variant of MMP12 is associated with increased lung...

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Veröffentlicht in:The New England journal of medicine Jg. 361; H. 27; S. 2599 - 2608
Hauptverfasser: Hunninghake, Gary M, Cho, Michael H, Tesfaigzi, Yohannes, Soto-Quiros, Manuel E, Avila, Lydiana, Lasky-Su, Jessica, Stidley, Chris, Melén, Erik, Söderhäll, Cilla, Hallberg, Jenny, Kull, Inger, Kere, Juha, Svartengren, Magnus, Pershagen, Göran, Wickman, Magnus, Lange, Christoph, Demeo, Dawn L, Hersh, Craig P, Klanderman, Barbara J, Raby, Benjamin A, Sparrow, David, Shapiro, Steven D, Silverman, Edwin K, Litonjua, Augusto A, Weiss, Scott T, Celedón, Juan C
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Waltham, MA Massachusetts Medical Society 31.12.2009
Schlagworte:
Adult
Aged
Alleles
Asthma - genetics
Asthma - physiopathology
Biological and medical sciences
Child
Chronic obstructive pulmonary disease, asthma
Cohort Studies
Disease management
Emphysema
Female
Forced Expiratory Volume - genetics
General aspects
Genetic Markers
Genetic Predisposition to Disease
Humans
Male
Matrix Metalloproteinase 12 - genetics
Medical research
Medical sciences
Middle Aged
Pneumology
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Pulmonary Disease, Chronic Obstructive - genetics
Pulmonary Disease, Chronic Obstructive - physiopathology
Risk factors
Smoking - genetics
Smoking - physiopathology
Human
Medicine
Lung disease
High risk
Lung function
Respiratory disease
Bronchus disease
Population
Chronic obstructive pulmonary disease
Obstructive pulmonary disease
ISSN:0028-4793, 1533-4406, 1533-4406
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Zusammenfassung:A variant of MMP12, encoding a matrix metallopeptidase, is associated with increased lung function in children with asthma and in adult smokers. It is also associated with a decreased risk of chronic obstructive pulmonary disease in adult smokers. A variant of MMP12 is associated with increased lung function in children with asthma and in adult smokers. It is also associated with a decreased risk of chronic obstructive pulmonary disease in adult smokers. MMP-12 (matrix metalloproteinase 12, also known as macrophage metalloelastase or matrix metallopeptidase 12 [Mmp12] in mice) is produced by macrophages, the predominant cell type that patrols the lower airspaces under normal conditions and the main inflammatory cell type that is recruited with smoking. 1 Mmp12 is essential for the development of emphysema in mice exposed to cigarette smoke, 2 including mice with increased expression of interleukin-13. 3 Increased expression of MMP12 in the lower airways can lead to degradation of elastin, resulting in elastin fragments that can cause a positive feedback loop, further increasing macrophage recruitment in mice 4 and in cultured human cells. . . .
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Drs. Hunninghake and Cho contributed equally to this article.
ISSN:0028-4793
1533-4406
1533-4406
DOI:10.1056/NEJMoa0904006