A gene that was hiding in plain sight appears to influence heart health and may lower the risk of heart attacks.
Researchers identified the gene by scanning the genetic information available from a biobank of thousands of Norwegians, focusing on variations in genes that change the way proteins function. Most of what they found turned out to be already known to affect cholesterol levels and other blood lipids.
But one gene, dubbed TM6SF2, wasn’t on the radar at all. In a minority of the Norwegians who carried a particular change in the gene, blood lipid levels were much healthier and they had a lower rate of heart attack.
And when the researchers boosted or suppressed the gene in mice, they saw the same effect on the animals’ blood lipid levels.
“Cardiovascular disease presents such a huge impact on people’s lives that we should leave no stone unturned in the search for the genes that cause heart attack,” says Cristen Willer, senior author of the paper published in Nature Genetics and an assistant professor at the University of Michigan Medical School.
“While genetic studies that focused on common variations may explain as much as 30 percent of the genetic component of lipid disorders, we still don’t know where the rest of the genetic risk comes from,” Willer adds. “This approach of focusing on protein-changing variation may help us zero in on new genes faster.”
Two diseases: heart and liver?
Willer and Kristian Hveem of the Norwegian University of Science and Technology led the team that published the new result. Intriguingly, Willer and colleagues suggest the same gene may also be involved in regulating lipid levels in the liver—a finding confirmed by the observations of a team led by Jonathan Cohen and Helen Hobbs, who propose a role for the gene in liver disease in the same issue of Nature Genetics.
Hveem, a gastroenterologist, says that “more research into the exact function of this protein will be needed to understand the role it plays in these two diseases, and whether it can be targeted with new drug therapies to reduce risk—or treat—one or both diseases.”
The success of the scientific experiment was due to efficient screening of thousands of Norwegian samples and clinical information amassed over a 30-year period by the Nord-Trøndelag Health Study (HUNT) and the Tromsø Study.
Lead author on the study, Oddgeir Holmen of Norwegian University of Science and Technology, adds, “These are exciting times for disease genetics. The combination of large population-based studies and the rapid development in genotyping technologies will probably help us understand a great deal more about cardiovascular disease, and other diseases, in the next few years.”
The HUNT Study is a collaboration between the HUNT Research Centre (Norwegian University of Science and Technology), the Nord-Trøndelag County Council, the Central Norway Health Authority, and the Norwegian Institute of Public Health. The US National Institutes of Health also provided funding.
Source: University of Michigan