Gene modifies severity of cystic fibrosis lung disease

Decided I need to start saving some articles I find really interesting and may want to refer back to so I dont have to keep hunting them down via link, blog, hard drive, hard copy what have you.

http://ec.europa.eu/research/headlines/news/article_09_03_25_en.html


Gene modifies severity of cystic fibrosis lung disease



Cystic fibrosis, the most common congenital disease, affects children's lungs, intestines and pancreas. While it is recognised that it is caused by a defect in a single gene, clogging the organs with thick mucus, an international team of scientists have identified a gene that modifies the severity of lung disease in people with cystic fibrosis. Their discovery can lead to new targets for treatment. The results of their study were recently published in the journal Nature.
Cystic fibrosis affects 70 000 people worldwide© ShutterstockThis study, according to the scientists, was key in strengthening cooperation amongst researchers and raising awareness about cystic fibrosis. 'This is a good example of researchers with different expertise coming together and using the knowledge gained from mapping the human genome to make discoveries that improve our understanding of cystic fibrosis,' said Dr Carl Langefield from Wake Forest University School of Medicine and co-author of the study.'It may also help in the identification of targets for drug development and the development of tools for the earlier diagnosis of individuals with cystic fibrosis who are susceptible to severe lung disease.'The group of scientists evaluated the genetic makeup of almost 3 000 cystic fibrosis patients. They discovered that small genetic differences in the IFRD1 (interferon-related developmental regulator 1) gene correlate with the severity of lung disease.The scientists also found that the protein encoded by IFRD1 is particularly abundant in neutrophils, a type of white blood cell, and it regulates their function. Neutrophils have been identified as triggering inflammatory damage in the airways of people suffering from cystic fibrosis.'Neutrophils appear to be particularly bad actors in cystic fibrosis,' explained Dr Christopher Karp from the Molecular Immunology at Cincinnati Children's Hospital Medical Center in the US, the senior investigator in this study. 'They are important to the immune system's response to bacterial infection. In cystic fibrosis, however, neutrophilic airway inflammation is dysregulated, eventually destroying the lung.'Past studies have shown that mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene trigger cystic fibrosis but questions remained over the molecular mechanisms that link these mutations to the generation of lung disease, the scientists said. According to them, the severity of cystic fibrosis lung disease can be controlled by the variations in other genes.The scientists assessed mice whose IFRD1 gene was removed and they confirmed its role in regulating inflammation and disease once it was removed. Bacteria are not quickly cleared away from the airway when the gene is missing.By checking the blood samples of healthy human volunteers, the team discovered that the same IFRD1 variations that altered the severity of cystic fibrosis lung disease also changed neutrophil function in the volunteers.They also found that IFRD1's regulation of neutrophil function depends on its interaction with the class of enzymes called histone deacetylases. The scientists said more information about this interaction is needed if it is to play a role in treating the disease.'It's possible that IFRD1 itself could become a target for treatment, but right now it's a signpost to pathways for further study,' Dr Karp explained. 'We want to find out what other genes and proteins IFRD1 interacts with, and how this is connected to inflammation in cystic fibrosis lung disease.'Cystic fibrosis affects 70 000 people worldwide and there is no known cure. Experts say the predicted median age of survival for a person with cystic fibrosis is 37 years, but with the introduction of new treatments this number can rise to 40 or even 50.Other institutions involved in the study were Biocenter, Division of Cell Biology at Innsbruck Medical University in Austria and the David Hide Asthma and Allergy Research Centre, Newport, Isle of Wight in the UK.