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Genetic Polymorphisms of Matrix Metalloproteinases

Functional Importance in the Development of Chronic Obstructive Pulmonary Disease?

  • Genomics In Human Disease
  • Published:
American Journal of Pharmacogenomics

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Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of global morbidity and mortality. COPD usually arises from an interaction between both host and environmental risk factors. Cigarette smoking is the major known environmental risk factor for the development of COPD, however, only a minority of smokers (approximately 15 to 20%) develop symptoms.

COPD is known to cluster in families, which suggests that there is a genetic predisposition to airflow obstruction. Many candidate genes have been assessed, but the data are often unclear. Here we review evidence that genetic polymorphisms in matrix metalloproteinase genes MMP1, MMP9 and MMP12 may be important in the development of COPD. In a Caucasian population, polymorphisms in the MMP1 and MMP12 genes, but not MMP9, have been suggested to be either causative factors in smoking-related lung injury or are in linkage disequilibrium with other causative polymorphisms. Another study found an association between an MMP9 polymorphism and the development of smoking-induced pulmonary emphysema in Japanese smokers.

Understanding the role of genetic polymorphisms in MMP1, MMP9 and MMP12 may help in the discovery of new and more effective therapies.

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Acknowledgements

Dr Wallace is supported by a Harry & Florence Dennison Fellowship in Medical Research. Dr Sandford was supported by a Parker B. Francis Fellowship and is a recipient of a Canada Research Chair in genetics.

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Correspondence to Alison M. Wallace.

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Wallace, A.M., Sandford, A.J. Genetic Polymorphisms of Matrix Metalloproteinases. Am J Pharmacogenomics 2, 167–175 (2002). https://doi.org/10.2165/00129785-200202030-00002

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