Researchers Identify Another Gene Variation That Increases Risk of Developing IPF

Iqra Mumal, MSc avatar

by Iqra Mumal, MSc |

Share this article:

Share article via email
IPF-linked gene variation

Researchers have identified a variation of the AKAP13 gene that they say increases people’s susceptibility to developing idiopathic pulmonary fibrosis.

An article about their discovery, published in The Lancet Respiratory Medicine, is titled “Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.

Previous studies have shown that there is a significant genetic component associated with the development of IPF. But the mechanisms through which these risk factors contribute to the disease has been unclear.

A group of international researchers set out to identify additional genetic variations that increase the risk of someone developing pulmonary fibrosis.

They conducted their research in two phases. First, they performed a genome-wide association study among ethnic European IPF patients at centers around the United Kingdom. A genome-wide association study involves combing through DNA for genetic variations linked to a disease — in this case, IPF.

The next step was to look at genetic variations in two datasets from the United States, one from a Chicago IPF consortium and the other from a Colorado consortium.

In the first phase, researchers examined 602 patients with IPF and 3,366 controls. The second phase covered 2,158 patients and 5,195 controls.

The analysis identified a previously unrecognized variation of a gene that makes people susceptible to IPF — the A-kinase anchoring protein 13 (AKAP13) gene. The team also confirmed previous findings that the MUC5B and DSP genes increase people’s susceptibility to IPF.

Researchers discovered that IPF patients with the allele A variation of the AKAP13 gene were more vulnerable to fibrosis, or tissue scarring, in their lungs after lung surgery than controls.

The AKAP13 gene codes for a protein that regulates a fibrosis signaling pathway. The allele A variation codes for a different form of the protein. This version accelerates the signaling process, leading to increased risk of IPF.

Scientists might be able to treat IPF by targeting the pathway, the research team said.

“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 Nottingham, the lead author of the study, said in a press release.

But more research is needed on the gene and its effects before scientists can begin developing a drug that targets 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.”