Genetic risk factors for chronic obstructive pulmonary disease

Abstract

Numerous epidemiologic studies have indicated that there is a genetic basis to COPD. This result suggests that COPD develops in genetically susceptible individuals after sufficient exposure to cigarette smoke. At present, most of the genes that contribute to the genetic component to COPD are unknown. alpha 1-Antitrypsin deficiency is clearly a risk factor for COPD, but the other genetic associations with this disease must be considered as tentative. The key to establishing that a gene modifies the risk for a disease is replication of the association in different populations. This is a difficult task, however, because different genetic risk factors may be present in different populations. In addition, these genetic factors may interact with each other and with environmental risk factors, obscuring the effect of the gene on the phenotype. Apart from alpha 1-AT only the GST-M1, VDBP and CFTR genes have been implicated as risk factors in more than one population. Identification of other candidate genes awaits further understanding of the pathogenesis of COPD at the molecular level. There is good evidence that the propensity to smoke cigarettes and the likelihood of quitting smoking are influenced by genetic factors. This information may be useful in efforts directed toward cessation; however, most of the genetic studies so far have shown a rather small effect. The responses to hypoxia and hypercapnia also seem to be influenced by genetic factors. Identification of the genes involved could yield important insights into the pathogenesis of COPD and may highlight new targets for therapeutic intervention for this debilitating disease.