02 April 2009

A Matter of Life and Breath


Single nucleotide mutations in a gene have recently been identified which may lead to poor lung development in children, increasing their vulnerability to toxins such as cigarette smoke, as well as the likelihood of acquiring diseases such as chronic obstructive pulmonary disease (COPD) during adulthood. Researchers in Germany and the United States have performed extensive research on the superoxide dismutase 3 (SOD3) gene, which is active in the extracellular matrix of the lung tissue (airway epithelial and alveolar type II cells). Previous research has shown SOD3 to protect the lungs from the effects of asbestos and oxidative stress, as well as promoting lung maturation during childhood.


The study used a mouse model in order to examine the levels of SOD3 in two different strains of mice with differing ventilation efficiency. The strain with superior ventilation efficiency showed high levels of SOD3 expression in the final stage of lung development, whereas the inferior strain showed a four-fold decrease in expression of the gene. In addition to this data, the mice with low expression of gene were found to have two common single nucleotide polymorphisms (SNP) (a single nucleotide base difference in the sequence of a gene) that were linked to lung function. These SNPs led to decreased SOD3 expression in the extracellular matrix of the lung, as well as decreased lung function. The study was then performed on 1555 children, aged 9-11 which yielded corresponding results.


These genetic variations have been associated with a decline in lung function in COPD, which is primarily caused by exposure to cigarette smoke. "We know SOD3 protects the lung against injury caused by chemicals in cigarette smoke, and it could be a link between childhood exposure to environmental tobacco smoke and poor lung development," said Dr. George Leikaf. Objectives of further research include being able to identify children with the mutation and developing a treatment to promote lung development.


References:
Collins, C. 2009, “Gene Changes May Stunt Lung Development in Children”, University of Pittsburgh, viewed 02 April 2009, http://www.medicalnewstoday.com/articles/143990.php.
Schulz et.al. 2009, “Superoxide dismutase 3, extracellular (SOD3) variants and lung function, viewed 02 April 2009, http://physiolgenomics.physiology.org/cgi/content/abstract/90363.2008v1.