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DNA sequence variations of metalloproteinases: their role in asthma and COPD

Department of Internal Medicine, Division of Pneumology, University Hospital of Patras, Patras, Greece

Correspondence to:
Correspondence to:
Kostas Spiropoulos
University Hospital of Patras, 26500, Rio, Patras, Greece; k-spiropoulos{at}hotmail.com

Asthma and chronic obstructive pulmonary disease (COPD) are complex genetic diseases that cause considerable morbidity and mortality worldwide. Genetic variability interacting with environmental and ethnic factors is presumed to cause tobacco smoke susceptibility and to influence asthma severity. A disintegrin and metalloproteinase 33 (ADAM33) and matrix metalloproteinase-9 (MMP9) appear to have important roles in asthma and COPD pathogenesis. ADAM33 and MMP9 genetic alterations could possibly contribute to the establishment and progression of these multifactorial diseases, although their association with the clinical phenotypes has not yet been elucidated. However, the occurrence of these alterations does not always result in clear disease, implying that either they are an epiphenomenon or they are in proximity to the true causative alteration. This review summarises the most recent literature dealing with the genetic variations of metalloproteinases and outlines their potential pathogenetic outcome.

Abbreviations: ADAM33, a disintegrin and metalloproteinase 33; BHR, bronchial hyper-responsiveness; COPD, chronic obstructive pulmonary disease; ECM, extracellular matrix; LD, linkage disequilibrium; MMP, matrix metalloproteinase; SNP, single nucleotide polymorphism

Keywords: ADAM33; asthma; COPD; genes; metalloproteinases; polymorphisms