Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find gene that modifies severity of cystic fibrosis lung disease

05.03.2009
Researchers at Wake Forest University Baptist Medical Center, and colleagues, have identified a gene that modifies the severity of lung disease in people with cystic fibrosis, a lethal genetic condition. The findings open the door to possible new targets for treatment, researchers say.

The study appeared online last week in advance of print publication in Nature. It is the first published study to search the entire genome looking for genes that modify the severity of cystic fibrosis lung disease.

"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 Carl Langefeld, Ph.D., a study co-author and Wake Forest University School of Medicine researcher. "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."

After analyzing the genetic makeup of nearly 3,000 cystic fibrosis patients, researchers found that small genetic differences in a gene called IFRD1 correlate with lung disease severity. While probing how the gene might alter the disease's course, researchers discovered the protein encoded by IFRD1 is particularly abundant in a type of white blood cell called neutrophils, and that it regulates their function. Part of the immune system, neutrophils are known to cause inflammatory damage to the airways of people with cystic fibrosis.

"Neutrophils appear to be particularly bad actors in cystic fibrosis," said senior investigator Christopher Karp, M.D., the director of Molecular Immunology at Cincinnati Children's Hospital Medical Center. "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."

Although it's been known for 20 years that cystic fibrosis is caused by mutations in the CFTR gene, the molecular mechanisms that link these mutations to the generation of lung disease still remain unclear. Increasingly evident in recent years is that variations in other genes also play a role in controlling cystic fibrosis lung disease severity.

Prior to the current study, IFRD1 was not really considered by researchers looking for genetic modifiers of disease severity, although the gene had been linked to stress responses in muscle and other tissues.

To further explore IFRD1's role in the disease process, the researchers studied mice in which the IFRD1 gene was removed. Deleting the gene confirmed its role in regulating inflammation and disease. While the absence resulted in delayed clearance of bacteria from the airway, it also resulted in less inflammation and disease.

The researchers also studied blood samples from healthy human volunteers to verify the impact of genetic differences in IFRD1 on neutrophil regulation. They found that the same IFRD1 variations that modified cystic fibrosis lung disease severity also altered neutrophil function in the healthy volunteers.

In a finding that may be the basis for novel approaches to treating cystic fibrosis, the investigators also determined that IFRD1's regulation of neutrophil function depends on its interaction with histone deacetylases – enzymes important for regulating gene transcription. Additional research is needed to better understand this interaction before its potential role for treatment is known, researchers report.

"It's possible that IFRD1 itself could become a target for treatment, but right now it's a signpost to pathways for further study," Karp said. "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."

According to the National Cystic Fibrosis Foundation, cystic fibrosis is an inherited chronic disease that affects the lungs and digestive systems of about 30,000 children and adults in the United States and 70,000 worldwide. The defect in the CFTR gene causes the body to produce unusually thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. It also obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.

In the 1950s, few children with cystic fibrosis lived to attend elementary school. Today, advances in research and medical treatments have allowed people to live into their 30s or 40s. Despite these advances, the norm remains an ongoing decline in pulmonary function.

Jessica Guenzel | EurekAlert!
Further information:
http://www.wfubmc.edu

More articles from Life Sciences:

nachricht New contents: Neuronal Parkinson inclusions are different than expected
26.06.2019 | Universität Basel

nachricht An ion channel with a doorkeeper: The pH of calcium ions controls ion channel opening
25.06.2019 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fraunhofer IDMT demonstrates its method for acoustic quality inspection at »Sensor+Test 2019« in Nürnberg

From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.

Reducing machine downtime, manufacturing defects, and excessive scrap

Im Focus: Successfully Tested in Praxis: Bidirectional Sensor Technology Optimizes Laser Material Deposition

The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.

Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Shell increases versatility of nanowires

26.06.2019 | Materials Sciences

Hubble finds tiny 'electric soccer balls' in space, helps solve interstellar mystery

26.06.2019 | Physics and Astronomy

New combination therapy established as safe and effective for prostate cancer

26.06.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>