Gene discovery could unlock the mysteries of fibrosis

Public Health

By Amanda Sheppeard

22 Sep 2016

Researchers have identified a gene variant linked to increased liver inflammation and fibrosis, paving the way for other organ diseases characterised by tissue scarring, including diseases of the heart, lungs and kidneys.

A large international team of researchers led by The Westmead Institute for Medical Research in Sydney say the new genetic variant identifies which chronic hepatitis C patients are at risk of developing liver disease.

In a paper published in the journal Nature Communications, the team lead by Professor Jacob George and Dr Mohammed Eslam from The Westmead Institute’s Storr Liver Centre describe their analysis of more than 2000 patients.

They found that a variant in the MBOAT7 gene is linked to increased liver inflammation, and thereby fibrosis (scarring).

Professor George told the limbic that the finding was significant, as it had the potential to be used to identify patients at greater risk of fibrosis than others.

“Forty five per cent of deaths today are due to scarring of the tissue,” he said.

This included diseases of the kidneys, heart, liver and lungs, he said.

“Irrespective of your disease, your body responds in fairly typical ways to inflammation – with scarring the result.”

The study showed that patients with the risk variant have low expression of MBOAT7 – a protective enzyme which reduces inflammation. With low expression, these patients have more severe liver inflammation and inflammatory markers in their blood.

Professor George said that the MBOAT7 gene could be the key to finding a treatment for a wide range of diseases.

“This gene is expressed by many immune cell types and is likely to be critical for the progression of inflammation and fibrosis irrespective of the organ,” he said. “That’s the big picture idea of where we want to go with this research.

“There is no reason why it couldn’t work with other diseases, this paper only focusses on Hep C.”

The MBOAT7 gene discovery adds another gene to the one identified last year by the same team as a marker for liver fibrosis progression.

Professor George told the limbic it was still very early days yet, but he hoped the gene could be eventually identified using a simple blood test. Currently the inexpensive test is costly due to the equipment and manpower required to complete it.

“This could be the key to finding a treatment for a wide range of potentially deadly conditions characterised by tissue scarring that can include diseases of the heart, lungs, and kidney, as well as the liver, he said.

Ultimately he said he hoped it could lead to the development of targeted anti-inflammatory or anti-fibrotic drugs that could be used as personalised medicine.

“I think we are slowly beginning to chip away in understanding inflammation and scarring,” he said.

“It’s early days still – we’re not saying this is the only gene that controls inflammation. There are probably 10 others that play some kind of a role.”

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