RESEARCHERS combined mouse and human data to identify the gene, which may reduce cholesterol production in the liver in response to a high cholesterol diet.
Cholesterol has several vital functions in the human body. For instance, the molecule is a component of cell membranes, and the body needs it to make vitamin D and some hormones.
However, excessive blood levels of cholesterol in the form of low-density lipoprotein (LDL) are a risk factor for atherosclerosis — the narrowing of the arteries due to the accumulation of fatty plaques — which can lead to a heart attack or stroke.
The body manufactures its own cholesterol in the liver, and rich dietary sources include eggs, red meat, and butter. Regardless of their diet, though, some people appear to be genetically predisposed to developing raised blood cholesterol levels.
“Unfortunately, we don’t really have a good understanding of how these genetic differences can drive differences in traits, whether that’s cholesterol or obesity,” says Brian Parks, a professor of nutritional sciences at the University of Wisconsin-Madison.
Prof. Parks led the new research, the findings of which may partly explain why some people have an inherited risk of developing high blood cholesterol. The work implicates a gene that normally reins in cholesterol production in the liver when dietary cholesterol intake is high.
The researchers went on to discover that Sestrin1 might shut down cholesterol synthesis in the liver when adequate amounts of cholesterol are available from the diet.
When they knocked out the gene in the livers of mice, the animals were unable to regulate cholesterol levels in their blood. They developed high cholesterol even when they ate a diet containing normally healthful amounts of the molecule.
The scientists say that larger studies will be necessary to confirm their results. However, they believe that their technique of combining mouse and human data has the potential to identify other genes that raise the risk of particular diseases.
Their method could offer new avenues for developing personalized or precision medicine, whereby doctors select the most effective treatments for people according to their genetic profile.
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