Israeli Researchers Discover Gene That Causes Liver Disease

The expression of the gene in an immune-system cell prevents the combating of liver scarring, heightening the risk of cirrhosis in drinkers and others.

Dan Even
Dan Even
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Dan Even
Dan Even

In a development that may have implications for alcohol drinkers, researchers at Hadassah Hospital have connected a particular gene to cirrhosis, or potentially life-threatening liver scarring.

The research team, led professor Rifaat Safadi, the head of the hospital's Liver Unit, found that people with a type of overexpression of a gene called Neuroligin 4 were predisposed to cirrhosis, which has many causes, including certain diseases and the consumption alcohol and some medications.

“We located a gene whose overexpression in the NK cells of the immune system exposes to the body to cirrhosis,” Safadi said. “When cirrhosis of the liver develops, the NK cells in the immune system, in their healthy form, kill the scar-tissue cells. We found that the overexpression of this gene put a mechanism into operation that kept these cells from their anti-scarring work.”

The tendency of some people to develop advanced cirrhosis has been a hot topic for investigation among liver-disease researchers in recent years.

The Hadassah study – which involved taking blood samples from dozens of patients with cirrhosis and comparing their NK cells to those of a control group of healthy people – came on the heels of related research. Several years ago, the same research team found that intact NK cells are good for the liver and prevent cirrhosis. The discovery, published in The Journal of Hepatology in February 2006, was also reported by a group of researchers at the National Institutes of Health in the United States.

Safadi's research team has also found a connection between the expression of Neuroligin 4 and insulin reception by cells throughout the body: Where there is insulin resistance, a precursor to diabetes that involves insulin receptors not working properly, the expression of Neuroligin 4 increases.

The findings were published in November 2012 at a conference of the American Association for the Study of Liver Diseases in Boston. Team member Dr. Johnny Amer was awarded the young researchers’ prize at the conference.

The Hadasit Technology Transfer Company of Hadassah Hospital has already patented Neuroligin 4 in hopes of using it to develop treatments to prevent liver disease. The gene has previously been connected with morbidity conditions and one of its mutations has been connected with the development of autism. Researchers next plan to investigate whether mutations of the gene also increase the risk of developing cirrhosis.

Dr. Rifaat Safadi, the head of Hadasah Hospital's Liver Unit.Credit: Avi Chayun

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