Gene-environment interactions in the development of chronic obstructive pulmonary disease.

PURPOSE OF REVIEW

Genetic factors influence the variable development of chronic obstructive pulmonary disease in response to smoking and are likely to vary between populations. Recent studies have begun to shed some light on these gene-environment interactions.

RECENT FINDINGS

A variety of approaches has been used to identify novel susceptibility genes for chronic obstructive pulmonary disease. These studies have provided evidence for the possible role of many inflammatory mediators and their receptors, proteases, antiproteases, and antioxidant and xenobiotic genes in chronic obstructive pulmonary disease pathophysiology. However, ethnic differences and subtle phenotype differences often make replication of these studies difficult.

SUMMARY

The completion of the Human Genome Project, the HapMap project, technological advances in single-nucleotide-polymorphism genotyping and the potential of genome-wide association analysis will allow the identification of susceptibility genes for chronic obstructive pulmonary disease. The challenge is to understand the influence of multiple genetic factors and multiple environmental factors as well as gene-gene and gene-environment interactions. Careful clinical characterization of phenotypes for chronic obstructive pulmonary disease is essential and this will include comparison of biomarkers of distinct pathologies including radiological assessment to separate the components of pulmonary emphysema and small-airway disease.