Genetics of Chronic Obstructive Pulmonary Disease

5 Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). However, not all smokers develop clinically significant symptoms. It is recognized that multiple genetic factors and genotype-by-environment interactions are involved in the development of COPD. Remarkable progress in the genetic knowledge and technology has changed the approaches used to identify candidate genes. Genome-wide linkage analyses have revealed several chromosomal regions linked to COPD phenotypes. The recently introduced gene expression profiling techniques have identified hundreds of genes differentially expressed in COPD. Case-control association studies have reported more than 30 polymorphisms related to the susceptibility to COPD. However, the replication of these results has been limited. In this review, we present our current understanding of the genetic basis of COPD and the findings of genetic studies. The advantages and limitations of the different genetic approaches are also discussed. The increasing knowledge of the COPD genetics combined with a better understanding of its clinical and pathological heterogeneity will have a great potential to change views on the pathogenesis and diagnosis, and even to influence the clinical management.