chapter  4
Pages 18

Case reports of familial COPD were published in the 1950s,1 but interest in the role of genetic factors in COPD largely began with the discovery of severe alpha-1antitrypsin deficiency in 1963.2 Severe alpha-1-antitrypsin deficiency is the most important known genetic determinant of COPD; therefore, we will discuss the molecular and population genetics of alpha-1-antitrypsin deficiency in detail. In addition, we will review the evidence for genetic factors in non-alpha-1-antitrypsin deficiency COPD, including assessment of risk to relatives for COPD-related phenotypes and association studies with candidate gene polymorphisms. We will also discuss the application of animal models to identify potential genetic determinants of COPD.