A new study entitled “Genes related to emphysema are enriched for ubiquitination pathways” published in BMC Pulmonary Medicine, aimed to determine the potential relationship between gene expression and specific phenotypes of chronic pulmonary disease (COPD).
Chronic obstructive pulmonary disease is defined by a combination of disease attributes of lung function, with studies indicating that are two distinct mechanisms contributing to the functional damage that COPD causes. These two mechanisms are chronic bronchiolitis with fibrosis that causes the narrowing of the small lung airways and emphysema that causes loss of lung elasticity. Although they are distinct mechanisms in COPD, they both lead to a reduction in maximal expiratory flow. Studies exploring molecular processes implicated in the development of diseases usually compare gene expression patterns in the organs of affected and non-affected samples. In the case of COPD, the gene expression patterns that may contribute to airway remodeling and to emphysema may de different, and evidence of a relationship between genetic determinants and these specific phenotypes of COPD is necessary, which can be more revealing than the comparison with the lung function.
To explore this association, a multisite team of researchers from the Covance Genomic Laboratory in Indianapolis, the Merck Research Laboratory in Rahway and The University of British Columbia Centre for Heart and Lung Innovation in Vancouver conducted an analysis in a sample of 21 smokers with airflow obstruction and different degrees of emphysema, as measured by the lung surface area to volume ratio (SA/V). The researchers identified 181 genes whose expression pattern correlated with the severity of emphysema. Then the researchers compared the expression of the genes with a separate set of 22 lung tissue samples, which served as a validation set. Measures included lung volumes, spirometry and single breath diffusing capacity.
Results of the study revealed a relationship in 30 of the 181 genes and the severity of emphysema (as measured by SA/V). Furthermore, this study pointed out the feasibility of gene set annotional and pathway analysis in the examination of this relationship, which determined that the genes implicated in the lung tissue samples with emphysema were those involving protein ubiquination and proteasome pathways. The analysis of the proteins revealed that in smokers’ obstructed lungs there is an over-accumulation of the protein ubiquination and an altered gene expression.