Cystic fibrosis can be deadly
Researchers have discovered a gene that modifies the severity of lung disease in people with the lethal genetic condition cystic fibrosis.
The US study, published by Nature, may aid development of new treatments.
The researchers deleted the key gene in mice, and then exposed the animals to a bacterium which often causes lung infections in cystic fibrosis patients.
The animals showed less sign of inflammation and disease than would otherwise be expected.
Around 8,000 people in the UK have cystic fibrosis and one in 25 are carriers for the condition.
Cystic fibrosis produces thick, sticky mucus that clogs the lungs and the pancreas, leading to life-threatening chest infections and problems with digestion.
Existing treatments only ease symptoms and life expectancy is low - most with people with cystic fibrosis die before they reach 40.
It has been known for 20 years that cystic fibrosis is caused by mutations in a gene called CFTR.
However, it has become apparent in recent years that other genes also play a role in determining the severity of lung disease associated with the condition.
The latest study started by analysing the genetic makeup of nearly 3,000 people with cystic fibrosis.
They found that small differences in a gene called IFRD1 correlated with the severity of lung disease the patients experienced.
White blood cells
Further analysis found that a protein produced by the gene appeared to play a key role in the function of a type of white blood cell called neutrophils.
These cells are part of the immune system and are known to trigger inflammatory damage to the airways of people with cystic fibrosis.
The researchers knocked out IFD1 in mice, and then exposed the animals to a bacterium called Pseudomonas aeruginosa, a common cause of airway infection in cystic fibrosis.
The animals took longer than normal to clear the bacteria from their airways - but they also showed less sign of inflammation and disease.
And although knocking out the gene blunted the inflammatory response of neutrophils to infection, it did not appear to affect other blood cells or compromise the overall functioning of the immune system.
Lead researcher Dr Christopher Karp, of Cincinnati Children's Hospital, said further work was needed to burrow down deeper into the molecular interactions.
He said: "It's possible that IFRD1 itself could become a target for treatment, but right now it's a signpost to pathways for further study.
"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."
A UK Cystic Fibrosis Gene Therapy Consortium spokesperson said it had been long suspected that genes other than CFTR played a role in determining the severity of cystic fibrosis.
"The result is important because it confirms the importance of other genes in modulating cystic fibrosis lung disease and implies that therapies aimed at modulating neutrophil function would have a beneficial effect in cystic fibrosis.
"Such therapies could eventually become a useful addition to the existing range of symptomatic therapies available.
"However, therapies aimed at correcting the basic defect in CF still offer the best prospect of providing long-term clinical benefit."