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- Title
The role of matrix metalloproteinasepolymorphisms in the rate of decline in lung function.
- Authors
Joos, Ladina; He, Jian-Qing; Shepherdson, MeganB.; Connett, JohnE.; Anthonisen, Nicholas R.; Paré, Peter D.; Sandford, AndrewJ.
- Abstract
The matrix metalloproteinases (MMPs) comprise a familyof at least 20 proteolytic enzymes that play an essential role intissue remodeling. MMP1 (interstitial collagenase), MMP9 (gelatinaseB) and MMP12 (macrophage elastase) are thought to be important inthe development of emphysema. A number of naturally occurring polymorphisms ofhuman MMP gene promoters have been identified andfound to alter transcriptional activity. Additionally, we detecteda 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 chronicobstructive lung disease. We determined the prevalence of thesepolymorphisms in 590 continuing smokers chosen from the NationalHeart Lung and Blood Institute, Lung Health Study for having thefastest (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 inlung function. The –1607GG allele was negatively associatedwith a fast rate of decline (P = 0.02).However, haplotypes consisting of alleles from the MMP1 G–1607GGand MMP12 Asn357Ser polymorphisms were associatedwith rate of decline of lung function (P = 0.0007).These data suggest that polymorphisms in the MMP1 and MMP12 genes, but not MMP9, areeither causative factors in smoking-related lung injury or are inlinkage disequilibrium with causative polymorphisms.
- Publication
Human Molecular Genetics, 2002, Vol 11, Issue 5, p569
- ISSN
0964-6906
- Publication type
Article
- DOI
10.1093/hmg/11.5.569