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

• Published in: The New England journal of medicine Vol. 361; no. 27; pp. 2599 - 2608
• Main Authors: 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
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 31.12.2009
• Subjects: 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
• DOI: 10.1056/NEJMoa0904006

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. . . .