Chronic Obstructive Pulmonary Disease (COPD) is a complex genetic disease in which multiple susceptibility genes and environmental factors interact to contribute to its development. Although there are two major approaches that can be used to identify susceptibility genes i.e. association studies and genomic scans, most of our knowledge of COPD genetics is derived from association studies. We review association studies of COPD that have examined genes involved in protease-antiprotease and oxidant-antioxidant balance, inflammation and airway defense. Currently, there are four major therapeutic approaches available: 1) Smoking cessation is the most important intervention to alter the clinical course, but only small proportion of smokers are able to quit successfully. Knowledge of genetic susceptibility may increase the rate of smoking cessation; 2) Therapy with bronchodilators; 3) Therapy with corticosteroids. The latter two approaches are the mainstay of current therapy. It has been shown that β2-adrenergic receptor (β2AR) gene polymorphisms affect β2-agonist therapy. However, no polymorphisms have been discovered that affect treatment with anticholinergics, theophylline or corticosteroids; 4) α1-antitrypsin (α1AT) replacement therapy is moderately effective in patients with α1-AT deficiency. New therapeutic methods based on knowledge of COPD genetics are urgently needed since current therapy has not been shown to prevent progression of COPD. Such methods may include protease inhibitors, mediator inhibitors and new anti-inflammatory agents. Thus, knowledge of COPD pharmacogenomics may help to tailor the most appropriate treatment for an individual patient.
Keywords: copd, genetics, polymorphisms, candidate gene, association study, genomic scan, pharmacogenomics, smoking cessation, alpha-1-antitrypsin, agonist
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