A team of scientists at the Mayo Clinic has discovered that a rare inherited gene mutation can directly cause a common liver disease that affects millions of people around the world. The finding challenges what doctors previously believed about how this disease develops and offers new hope for better diagnosis and treatment in the future.
The disease is called metabolic dysfunction-associated steatotic liver disease, often shortened to MASLD. It was previously known as nonalcoholic fatty liver disease. This condition happens when too much fat builds up in the liver of people who drink little or no alcohol. Over time, the fat can damage the liver and lead to serious health problems.
MASLD is extremely common. Scientists estimate that about one-third of adults worldwide have some form of the disease. In many people, the condition remains mild, but in others it becomes much more serious.
A more severe stage of the disease is called metabolic dysfunction-associated steatohepatitis, or MASH. In this stage, fat buildup causes inflammation and injury to liver cells.
If the disease continues to progress, the liver may develop fibrosis, which means scar tissue forms in the organ. Eventually this scarring can become severe, leading to cirrhosis. Cirrhosis makes the liver stiff and unable to perform its normal functions. In the most advanced cases, cirrhosis can lead to liver failure or liver cancer.
For many years, doctors believed that MASLD developed mainly from a combination of lifestyle factors and common genetic risks. Being overweight, having diabetes, or having high cholesterol are known to increase the risk. Poor diet and lack of exercise also play an important role.
However, the new research suggests that in some people, a single rare genetic mutation can be the main reason the disease develops.
The study was led by researchers at the Mayo Clinic’s Center for Individualized Medicine and was published in the scientific journal Hepatology.
The discovery began when doctors studied a woman and her father who both had severe fatty liver disease. What made their cases unusual was that they did not have the common risk factors typically linked with the condition. Neither of them had diabetes, and their cholesterol levels were normal.
Because their cases did not fit the usual pattern, researchers decided to look more closely at their genetic makeup. Using advanced genomic technology, scientists examined more than 20,000 genes in their DNA.
During this search, the researchers found a small but important change in a gene called MET.
Genes are made of chemical instructions that tell the body how to build and maintain tissues. The MET gene plays an important role in liver repair and in how the body processes fats. When this gene works normally, it helps liver cells recover from injury and manage fat levels properly.
In the affected family, scientists discovered that one tiny change in the MET gene disrupted this process. The mutation involved a single change in the DNA code, but it had a powerful effect. Because the gene was altered, the liver could not process fats correctly.
As a result, fat began to accumulate inside liver cells. This buildup of fat triggered inflammation and damage in the liver, which eventually led to fatty liver disease.
Researchers confirmed that this mutation had never been reported before in scientific literature or public genetic databases. This made the discovery especially important.
Dr. Filippo Pinto e Vairo, one of the lead researchers, explained that this discovery helps scientists better understand how rare genetic changes can sometimes cause diseases that appear very common.
The research team also worked with scientists from the Medical College of Wisconsin to confirm how the mutation interfered with the body’s biological processes.
After identifying the mutation in the family, the researchers wanted to know whether similar genetic changes might exist in other people with fatty liver disease.
To answer this question, they turned to a large research project called the Tapestry study. This project collects genetic information from volunteers across the United States in order to understand how genes influence health and disease.
The Tapestry study has already analyzed DNA from more than 100,000 people, creating one of the largest genetic databases of its kind.
When scientists examined the genetic data of nearly 4,000 people with MASLD in the Tapestry database, they found something interesting. About one percent of these individuals carried rare variants in the same MET gene.
Even more striking, nearly eighteen percent of these variants occurred in the same important region of the gene that had been identified in the original family.
This finding strengthened the evidence that changes in the MET gene may play a significant role in causing fatty liver disease in some people.
Dr. Konstantinos Lazaridis, another senior researcher involved in the study, said that discoveries like this show how powerful large genetic databases can be for uncovering hidden causes of disease.
The study also highlights the growing importance of precision medicine. Precision medicine focuses on understanding the unique genetic and biological factors that affect each individual patient. Instead of treating every patient the same way, doctors can use genetic information to tailor diagnosis and treatment more accurately.
At the Mayo Clinic, researchers are increasingly using advanced genomic tools to solve medical mysteries. Since 2019, the clinic’s Program for Rare and Undiagnosed Diseases has provided more than 3,200 patients with access to detailed genetic testing.
Nearly 300 doctors and specialists work together in this program to identify rare diseases and difficult medical conditions.
The discovery of the MET gene mutation provides an important new clue about how fatty liver disease can develop. It also opens the door for future research into new treatments that may target this genetic pathway.
In the future, doctors may be able to use genetic testing to identify patients who carry similar mutations. This could allow earlier diagnosis and more personalized treatments before severe liver damage occurs.
The findings also suggest that what appears to be a common disease may sometimes hide rare genetic causes. Understanding these hidden causes could help scientists design better therapies and prevention strategies.
Overall, the study shows how combining family-based research with large genetic databases can uncover important discoveries about human health. As genomic medicine continues to advance, researchers hope to reveal more of the hidden genetic factors behind major diseases and develop new ways to treat them.
If you care about liver health, please read studies that refined fiber is link to liver cancer, and the best and worst foods for liver health.
For more health information, please see recent studies about how to boost your liver naturally, and simple ways to detox your liver.
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