As scanning genomes for disease-related gene variations becomes more commonplace, scientists are pinpointing gene variations that change the way proteins function. Using this approach, a new study found a previously unknown gene variation that appears to make blood lipid levels healthier in humans and reduce risk of heart attacks.
The study researchers, from the University of Michigan and the Norwegian University of Science and Technology, report their findings in Nature Genetics. They hope the discovery will lead to new ways of testing or treating patients with high cholesterol and other lipid disorders.
They explain that by looking at the genetic code differently - such as looking for how it influences the way proteins behave - they found the gene hiding in plain sight in previous searches for cardiovascular risk genes.
Senior author Cristen Willer, assistant professor of Internal Medicine, Human Genetics and Computational Medicine & Bioinformatics at the University of Michigan Medical School, says:
"While genetic studies that focused on common variations may explain as much as 30% of the genetic component of lipid disorders, we still don't know where the rest of the genetic risk comes from. This approach of focusing on protein-changing variation may help us zero in on new genes faster."
Several members of the team had been involved in earlier research in 2008 that looked at the same region of DNA and found it was linked to control of blood lipid levels.
But there was no suggestion at the time that this region of DNA contained specific genes with an obvious link to blood lipid levels.
Now, some 6 years later, the researchers scanned the genomes of over 5,600 Norwegians whose genetic, medical and health data was housed in a biobank. They focused on searching for variations in genes that change the way proteins function - in all, identifying over 80,000 coding variants.
From these, they came up with 18 candidate variants that they narrowed down to 10 that had links to blood lipid traits. Most of what they found was already known to be linked to cholesterol and other blood lipid levels.
Gene 'hiding in plain sight' in previous searches for cardiovascular risk genes
But one gene, TM6SF2, was a completely new find that had not surfaced before, although it had been "residing in a known genome-wide association study locus for lipid traits," write the authors.
A small percentage of the Norwegian participants who carried a particular variant of this TM6SF2 gene had noticeably healthier levels of blood lipids, and a significantly lower rate of heart attack.
In another part of the study, the team tested what happened when the gene was overexpressed or silenced in mice. The result was the same as they had seen in humans - the animals' blood lipid levels were healthier when the gene was present.
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