Gene study helps understand pulmonary fibrosis

April 16, 2013

A new study looking at the genomes of more than 1,500 patients with idiopathic pulmonary fibrosis, a rare and devastating lung disease, found multiple genetic associations with the disease, including one gene variant that was linked to an increase in the risk of death.

The study, released early online in The Lancet Respiratory Medicine, showed that a variant in a gene called TOLLIP was associated with an increased . That variant resulted in decreased expression of TOLLIP in the lungs of patients with idiopathic (IPF).

Because TOLLIP, also known as toll interacting protein, plays a role in regulating immunity to certain stimuli, this novel finding suggests that an abnormal , possibly to or even environmental injury, may be central to the disease.

Curiously, the version of TOLLIP that appears to prevent onset of the disease was also the variant that increased the risk of death in patients who did develop IPF.

"Our initial -wide study revealed 20 that may be associated with this disease," said lead author Imre Noth, MD, professor of medicine and director of the Interstitial Lung Disease Program at the University of Chicago. "A more focused investigation showed that four of these play a crucial role."

The researchers confirmed one previously implicated gene tied to disease onset and, more important, found the new that appears to play a role in both onset and mortality.

The results "change our perception of the importance of genetics in IPF," Noth said. "Preliminary work, looking at multiple variants of different genes, may allow us to predict the risk of death in IPF patients, which can vary according to their genetics up to 6.5 fold. This would be a powerful prognostic test."

Idiopathic pulmonary fibrosis affects about 150,000 people in the United States, usually after age 50. It causes progressive scarring of the lungs, which leads to increasing difficulty with breathing. For most patients, this leads to death, usually within three to five years. The only effective therapy is a lung transplant.

"The finding that one of the TOLLIP gene variants is reproducibly linked to higher mortality in IPF patients has significant implications for patient management," noted co-senior author Naftali Kaminski, MD, professor of medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, and director of UPMC's Dorothy P. and Richard P. Simmons Center for .

"If an IPF patient has this variant, we might want to consider lung transplantation early in the course of the disease," he said. "It's not an ideal treatment, but it saves lives. We might be able to use the genetic markers to reveal who might need a transplant quickly, and to stratify patients for research."

One way to learn more about a complex disease such as IPF is through large-scale studies to search for genetic variations that are more common in those with the disorder. In many cases, the results of a single study are not replicated.

To address this concern, the multi-institution research team looked for links between genetic markers and IPF in three separate cohorts of patients. The results were consistent in all three groups, highlighting the reproducibility of the results that could now provide investigators with a better understanding of what causes IPF.

"The findings of this study open new avenues for IPF research" noted co-senior author Joe G.N. Garcia, MD, professor and director of the Institute for Personalized at the University of Illinois at Chicago and vice president for health affairs at the University of Illinois Hospital & Health Sciences System. "Researchers can now focus on understanding the role of the variants found in humans, and drug companies can assess whether they already have drugs that affect these pathways, thus shortening the lag to new therapeutics."

"IPF is a relentless disease for which we have no effective therapies to control or reverse the progressive scarring that leads to the untimely deaths," added James Kiley, PhD, Director of the Division of Lung Diseases at the National Heart, Lung and Blood Institute, part of the National Institutes of Health, which partially funded this study. "Insights from basic research like this are what we need to develop therapies that target the underlying disease process."

Explore further: Common genetic variant linked to pulmonary fibrosis risk

More information: The paper, "A Genome-wide Association Study Identifies Novel Genetic Variants in Association with Idiopathic Pulmonary Fibrosis Susceptibility and Mortality," will be published in the May issue of The Lancet Respiratory Medicine.

Related Stories

Common genetic variant linked to pulmonary fibrosis risk

April 20, 2011
Scientists funded by the National Institutes of Health have identified a common genetic variant associated with substantially increased risk of developing pulmonary fibrosis, a debilitating and life-threatening lung condition. ...

Delayed access to tertiary care associated with higher death rate from type of pulmonary fibrosis

July 1, 2011
Idiopathic pulmonary fibrosis (IPF)―scarring and thickening of the lungs from unknown causes―is the predominant condition leading to lung transplantation nationwide. Columbia University Medical Center researchers ...

Blood proteins predict survival in idiopathic pulmonary fibrosis: study

October 25, 2011
A panel of blood proteins can predict which patients with the progressive lung disease idiopathic pulmonary fibrosis (IPF) are likely to live at least five years or to die within two years, say researchers at the University ...

Genetic variation contributes to pulmonary fibrosis risk

April 15, 2013
A newly published study of patients with pulmonary fibrosis has discovered multiple genetic variations that should help with future efforts to treat the disease.

Recommended for you

Google searches can be used to track dengue in underdeveloped countries

July 20, 2017
An analytical tool that combines Google search data with government-provided clinical data can quickly and accurately track dengue fever in less-developed countries, according to new research published in PLOS Computational ...

MRSA emerged years before methicillin was even discovered

July 19, 2017
Methicillin resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to a study published in the open access journal Genome Biology. It was ...

New test distinguishes Zika from similar viral infections

July 18, 2017
A new test is the best-to-date in differentiating Zika virus infections from infections caused by similar viruses. The antibody-based assay, developed by researchers at UC Berkeley and Humabs BioMed, a private biotechnology ...

'Superbugs' study reveals complex picture of E. coli bloodstream infections

July 18, 2017
The first large-scale genetic study of Escherichia coli (E. coli) cultured from patients with bloodstream infections in England showed that drug resistant 'superbugs' are not always out-competing other strains. Research by ...

Ebola virus can persist in monkeys that survived disease, even after symptoms disappear

July 17, 2017
Ebola virus infection can be detected in rhesus monkeys that survive the disease and no longer show symptoms, according to research published by Army scientists in today's online edition of the journal Nature Microbiology. ...

Mountain gorillas have herpes virus similar to that found in humans

July 13, 2017
Scientists from the University of California, Davis, have detected a herpes virus in wild mountain gorillas that is very similar to the Epstein-Barr virus in humans, according to a study published today in the journal Scientific ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.