Genetics of chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex disease with multifactorial background, based on the interaction of environmental and genetic factors. Environmental factors are clearly related to the development of the disease. However, family and twin studies suggested genetics factors to be one of the important determinants for the development of COPD. Different approaches have been used to identify genes of interest. Genomewide linkage analysis found areas of interest on different chromosomes, with some genes located in this regions being identified and replicated as susceptibility genes. Numerous of candidate genes that could be linked to disease pathogenesis have been implicated in COPD genetics. However, the candidate gene approach is often limited by inconsistent results in other study populations. Recently, a combination of different methods is used giving more evidence for some candidate genes, including TGFbeta-1, Surfactant, SERPINE2 and microsomal epoxide hydrolase. In the future ongoing exact phenotype definition, combination of several approaches, genome-wide association studies and animal model genetics will lead to new insights into the genetics of COPD, with epigenetic factors needs to be further investigated and considered in concert with genetic findings.

Figure 1

Graphical depiction of cells and mediator systems involved in COPD pathogenesis. Oxidative stress, inflammation and proteolysis and their opponents are the important components influencing disease pathogenesis.

Figure 2

Shows graphically the principle of gene expression profiling using cDNA microarrays. The activity of up to 20000 genes could be simultaneous evaluated. Usually two tissues or cell populations are compared and the final result shows the different genetic activity of the sample of interest compared to a reference control.