Image: Illumina HiSeq 2500 ultra-high-throughput sequencing system (Photo courtesy of Konrad Förstner).
A previously unrecognized gene variation that makes humans have healthier blood lipid levels and reduced risk of heart attacks has been found.
The region of DNA where it was located had been implicated as being important in controlling blood lipid levels, but although this DNA region had many genes, none of them had any obvious link to blood lipid levels.
A team of scientists from the University of Michigan (Ann Arbor, Michigan, USA) and the Norwegian University of Science and Technology (Levanger, Norway) scanned the genetic information available from a biobank of a large number 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. Total cholesterol (TC), high density lipid (HDL) cholesterol and triglycerides were measured by an enzymatic colorimetric method using the 911 Auto-Analyzer (Hitachi; Tokyo, Japan).
Genotyping of 5,771 individuals was performed using the Human Exome BeadChips (Illumina; San Diego, CA, USA) using their Infinium HD ultra protocol. The exome array includes 247,870 markers focused on protein-altering variants. Low-pass whole-genome sequencing was performed with exome enrichment on 76 cases with myocardial infarction (MI) and 76 controls using Illumina’s Hi-Seq 2500 ultra-high-throughput sequencing system. In a minority of the Norwegians who carried a particular change in a gene, blood lipid levels were much healthier and they had a lower rate of heart attack. This gene, known as Transmembrane 6 Superfamily Member 2 (TM6SF2), may also be involved in regulating lipid levels in the liver.
Cristen Willer, PhD, the senior author of the paper, said, “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. 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.” The study was published on March 16, 2014, in the journal Nature Genetics.
University of Michigan
Norwegian University of Science and Technology