Scientists have identified a variation of a gene that they say makes a person susceptible to developing idiopathic pulmonary fibrosis.
The discovery raises the possibility of developing an IPF therapy that targets the AKAP13 gene variation.
Although IPF is a serious disease with a poor patient prognosis, little is known about the mechanisms that lead to it. Scientists have identified only a few genetic risk factors associated with IPF. And they have yet to identify the molecular mechanisms by which these genetic risk factors lead to IPF.
British scientists decided to try to identify more genetic risk factors associated with IPF and investigate the mechanisms involved.
Their research, “Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study,” was published in The Lancet Respiratory Medicine.
The team used a genome-wide association study (GWAS) approach to analyze data from published research. GWAS involves searching the genome — or complete set of DNA — for genetic variations that might occur more frequently in people with a disease than in those without the disease.
Researchers compared the genomes of 602 IPF patients with those of 3,366 controls to identify genetic variations associated with IPF. Then they looked for the variations in 2,158 other IPF patients and 5,195 other controls.
Previous studies had already identified many of the IPF-linked variations that the team found — those in the MUC5B and DSP genes, for example.
But the team found variations of a gene that had not been linked to IPF. This gene, AKAP13, codes for a protein known as A-kinase anchoring protein 13, or AKAP13. Previous studies had shown that the protein plays a role in fibrosis signaling pathways that lead to tissue scarring.
To link AKAP13 to mechanisms leading to IPF, the team looked at levels of the protein in tissue samples from IPF patients. They discovered that AKAP13 levels were higher in the epithelial lung cells of IPF patients with a variation of the AKAP13 gene than in patients without the variation. Epithelial cells line lung cavities.
The evidence suggested that AKAP13 is associated with the disruption of the signaling pathway — a dysfunction that triggers IPF. This means that targeting the pathway could be a way to treat IPF.
“What is really exciting about these studies is that this gene affects a pathway that can be targeted by drugs currently in development, opening the door to precision medicine in IPF,” Professor Gisli Jenkins of the University of Nottingha, one of the lead authors of the study, said in a press release.
But additional studies of the AKAP13 gene’s role in the development of IPF are necessary before scientists start developing therapies targeting the pathway, the team said.
“We urgently need new ways to treat this terrible disease,” said Professor Louise Wain, the GlaxoSmithKline British Lung Foundation Chair of Respiratory Research at the University of Leicester. “Our findings highlight a potential new avenue for treatment, and we now need more research to identify why this gene is important in IPF and how we can use that information to identify new therapies.”
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