Gene mutation reduces blood lipids

People who carry a certain gene mutation can break down harmful lipoproteins more easily than others. This is the surprising discovery from researchers in the Netherlands and Linköping now being published in the journal Cell Metabolism.

The lipoproteins HDL and LDL play an important role in regulating the body’s lipoproteins. People with high HDL, the ‘good’ cholesterol, often have low lipoproteins, thereby running less risk of cardiovascular disease, while the opposite is true with LDL.

Geneticist Jan Albert Kuivenhoven, at the University of Groningen, studied two families whose members had unusually high HDL content and low lipoprotein, or triglyceride, content. When the people were screened for a number of suspected genes, a mutation on the GALNT2 gene was discovered.

When the people carrying the mutation were given pure cream to drink, it turned out that they broke down the triglycerides better than those who had the functioning gene.

“The hypothesis was that the mutation was the reason for the family members’ favourable profile. Our task was to review the proteins in their blood plasma to see if there was anything unusual. We then found a deviant form of the APO C-III protein,” says Helen Karlsson, MD, in Work and Environmental Medicine at Linköping University.

The normal form of this protein inhibits the breakdown of lipoproteins in the blood. But when the GALNT2 gene mutates, APO C-III changes and the inhibition decreases. The consequence is that the lipoproteins are broken down faster.

“This shows that we can have different genetic conditions for breaking down lipoproteins. It’s too early to say that these individuals are at less risk for developing cardiovascular disease, but our discovery could be a possible new goal in the search for medicine that reduces triglycerides and increases the good cholesterol,” Karlsson says.

The work is a part of the EU project around the function of HDL, in which Karlsson and senior lecturer Mats Lindahl are cooperating with the Dutch group.

Article: A.G Holleboom, H. Karlsson et al: Heterozygosity for a loss-of-function mutation in GALNT2 improves plasma triglyceride clearance in man. Cell Metabolism 14:6, 7 December 2011
Contact: Helen Karlsson, MD +46 (0) 73-6442338
 

Åke Hjelm 2011-12-13