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Study Pinpoints New Gene for Cystic Fibrosis
Date:2/25/2009

Variant can affect disease severity, experts say,,

WEDNESDAY, Feb. 25 (HealthDay News) -- Researchers have identified a new gene associated with cystic fibrosis.

Dr. Christopher Karp, of the Cincinnati Children's Hospital Medical Center, and an international team of colleagues demonstrated that variants in a gene called IFRD1 can modulate the airway disease that marks cystic fibrosis (CF) by muting the pro-inflammatory activities of white blood cells called neutrophils.

Crucial in clearing bacterial infections, neutrophils have long been suspects in CF airway disease, Karp said. It was thought that they damage the airway via a hyperactive response to the persistent bacterial infections that plague people with CF.

"I think the significance of the paper is it further strengthens the importance of neutrophil function in modulating disease severity," said Chris Penland, director of research at the Cystic Fibrosis Foundation, which partially funded the study.

Though it's too early to recommend changes in genetic screening or counseling, the findings do implicate IFRD1 in particular, and neutrophil activation in general, as potential targets for drug development.

The results were published online Feb. 25 in Nature.

Researchers have long known that mutations in the gene CFTR were associated with cystic fibrosis, but were unable to account for the spectrum of lung disease severity that accompanies the disease.

That, Karp said, suggested two possibilities: "Either that there are strong environmental influences, and/or there are other genes that modify the expression of lung disease in cystic fibrosis."

A handful of modifiers had already been identified, all related to immune cell function. To identify additional candidates, Karp and his team scanned 100,000 genetic markers, called single nucleotide polymorphisms, across the genomes of two large cohorts of people with
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