Genetic susceptibility to tobacco smoke toxicity and chronic obstructive pulmonary disease

Because elderly patients with chronic obstructive pulmonary disease are often overlooked, screening efforts are at the moment directed at higher risk subjects such as heavy smokers with obstructive airways disease. Because only 10–20% of heavy smokers developed symptomatic airflow obstruction, a different genetic susceptibility to cigarette smoke‐lung injury is implicated in the pathogenesis of chronic obstructive pulmonary disease. Several candidate gene polymorphisms are proposed as the genetic risk for the development of chronic obstructive pulmonary disease. The current candidates are the polymorphisms in the 3′ non‐coding region of the α 1‐antitypsin gene, α 1‐antichymotrypsin gene, tumor necrosis factor‐ α gene , microsomal epoxide hydrolase gene, and glutathione S‐ transferase P1 gene, and microsatellite polymorphism in the heme oxygenase‐1 gene promoter. However, the results are variously reported between Japanese and Caucasians. The association studies of the polymorphisms with chronic obstructive pulmonary disease require further confirmation in different ethnic groups by other researchers using a large population. The current strategy and pitfalls of the gene explorations of chronic obstructive pulmonary disease are discussed.