Precision Medicine News

Gene Linked to Cholesterol Regulation Could Boost Precision Medicine

By combining data from human and animal studies, researchers have discovered a gene that could advance precision medicine for cholesterol-related diseases.

Gene linked to cholesterol regulation could boost precision medicine

Source: Getty Images

By Jessica Kent

- A team from the University of Wisconsin-Madison has uncovered a gene involved in regulating the body’s cholesterol, which could help advance precision medicine treatments for heart disease and other cholesterol-related conditions.

Developing drugs that can target a patient’s unique genetic sequence requires knowing which genes are involved in disease, which can be a challenging process.

“Unfortunately, we don’t really have a good understanding of how these genetic differences can derive differences in traits, whether that’s cholesterol or obesity,” said Brian Parks, a professor of nutritional sciences at the University of Wisconsin–Madison.

In a study published in the journal Cell Metabolism, the team combined details available from animal studies with genetic studies containing hundreds of thousands of genome studies.

Researchers used mouse livers to investigate genetic networks involved in cholesterol synthesis, which provided data that is rarely available in humans. The group identified 112 genes linked to known cholesterol genetic networks.

Researchers then looked to see which of those 112 genes overlapped with potential cholesterol-linked DNA sequences in humans. The team collected the human data from massive genetic studies that analyze data to try and find a link between genes and disease.

“We can do these very large studies in humans of 500,000 people, and we can identify regions of the genome that are associated with, say, differences in blood cholesterol,” said Parks. “But that just gives us kind of a lamppost to shine a light. It doesn’t tell us what underlying gene or pathway is potentially contributing to that association.”

Of the 112 genes they started with, the team found that 54 had ties to human data. Twenty-five had not been previously linked to cholesterol levels in humans, which made them potential new targets.

“Most of them are well-known to be involved in cholesterol or liquid metabolism. But we were interested in the ones that were unknown,” said Parks.

The team studied those 25 genes in mouse models and compared them with fresh batches of human genomic data. Researchers found that one gene, Sestrin1, helps regulate cholesterol levels in the blood. The gene promotes cholesterol synthesis until it’s shut off by cholesterol from the diet.

Mice that were missing the gene were unable to regulate cholesterol levels properly, and developed high cholesterol when consuming diets made up of normal levels of cholesterol because their livers didn’t respond properly.

These results could provide a new target for understanding the genetic risk of high cholesterol, leading to precision medicine treatments for heart disease and other conditions. Additionally, the study offers a new method to find out how genetic variation underlies a number of human diseases, which is the first step toward treating them.

Researchers noted that they had an advantage in studying cholesterol, because it is primarily controlled by just one tissue – the liver. However, the method of using both human and animal data to uncover previously unknown genes could help shed light on other conditions, researchers noted. This approach could be extremely valuable for understanding and treating disease.

“The possibility certainly exists to extend this technique to other traits like obesity,” said Parks.