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Scientists find gene that modifies severity of cystic fibrosis lung disease
Date:3/3/2009

entually 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."

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Contact: Jessica Guenzel
jguenzel@wfubmc.edu
336-716-3487
Wake Forest University Baptist Medical Center
Source:Eurekalert

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