Genetic predisposition to accelerated decline of lung function in COPD.
Environmental exposures and genetic susceptibility can contribute to lung function decline in chronic obstructive pulmonary disease (COPD). The environmental factors are better known than the genetic factors. One of the commonest reasons of accelerated forced expiratory volume in one second (FEV1) decline in COPD is the continuation of the smoking habit. In addition, COPD patients have frequent acute respiratory infections which can also accelerate the decline of FEV1. All of the gene variants that have been reported in association with accelerated decline of lung function in COPD represent advancement because the findings generate plausible hypotheses about the possible mechanisms by which gene products could accelerate or avert FEV1 decline. Unfortunately, the results have not been consistently replicated and, animal models required to functionally assess the genetic findings, have not yet yielded sufficient data. Genome-wide association studies should provide more definitive results in COPD and other multigenic conditions. Until these studies are reported, the data to date suggest that products encoded by the alpha-1 antitrypsin, some matrix metalloproteinases, and a number of antioxidant genes are associated with accelerated FEV1 decline in COPD. Data on gene variants associated with acute exacerbations of COPD are now emerging.
Otsuka Maryland Research Institute, Rockville, MD 20850, USA. nestorm@otsuka.com
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Molfino
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D018450:Disease Progression; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D012141:Respiratory Tract Infections / Q000150:complications; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D000515:alpha 1-Antitrypsin / Q000235:genetics
D000975:Antioxidants; D000515:alpha 1-Antitrypsin; D020782:Matrix Metalloproteinases