Danish researchers establish link between gene and ‘good cholesterol’ – University of Copenhagen

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08 September 2016

Danish researchers establish link between gene and ‘good cholesterol’

Cholesterol

Danish researchers are the first in the world to have finally established a link between the GALNT2 gene and the level of HDL cholesterol – otherwise known as ‘good cholesterol’. This paves the way for continued research into whether the regulation of this gene can affect the risk of arteriosclerosis and cardiovascular diseases.

Danish researchers are the first in the world to have just demonstrated a link between the GALNT2 gene and the level of high-density lipoprotein cholesterol (HDL-C). A low level of HDL-C in the body increases the risk of arteriosclerosis and cardiovascular diseases, which makes it useful to know which mechanisms in the body help regulate it. So far however, there have been doubts among researchers about the extent to which the GALNT2 gene has helped to raise or lower the cholesterol, but Danish researchers now have the answer.

“We wanted to understand the role that GALNT2 plays in regulating the level of HDL-C in the blood. Based on existing literature, we have not been able to determine whether GALNT2 contributes to raising or lowering HDL-C levels. By taking a closer look at the mechanisms taking place in our cells, we can now conclude that a low or non-existent level of GALNT2 activity is linked to low levels of HDL-C,” says Assistant Professor Katrine Schjoldager, Copenhagen Center for Glycomics, University of Copenhagen.

Several species and new technologies refine results
To study the effect of a gene, researchers often use mice as animal models. However, as something quite unique, the Danish group of researchers has studied the effect of GALNT2 in several different species: mice, rats, monkeys and humans. For the first time ever, researchers have identified people with a GALNT2 gene deficiency, and they have also used new gene technology tools to remove the gene in mice, rats and monkeys.

“It’s the first time that we’re able to study GALNT2 and HDL across species. Moreover, it’s the first time that we have the competencies and the technological tools needed to go in and characterise the function of a gene like GALNT2. GALNT2 is one of many enzymes that attach sugar to proteins and regulate the proteins’ functions, so it is particularly difficult to identify specific causal relationships. We have now shown that GALNT2’s functions are causal for the HDL level. This is of considerable importance for research into similar mechanisms, and may have a significant impact on research into the extent to which the regulation of GALNT2 can affect the level of HDL-cholesterol and thus also the risk of developing arteriosclerosis and cardiovascular diseases,” says Katrine Schjoldager, while emphasising that studies of this kind will not be taking place in the immediate future.

The study is a collaboration between the Copenhagen Center for Glycomics at the University of Copenhagen, the Perelman School of Medicine at the University of Pennsylvania and the American pharmaceutical company Bristol-Myers Squibb as well as a number of other institutions. The Danish researchers have also been working with a team of leading heart researchers from the USA, but they have also visited France, Morocco and Germany to collect samples for the study. The findings of the study have just been published in Cell Metabolism and can be read here.

Contact:
Assistant Professor Katrine Schjoldager, mobile: +45 2384 0150, email: schjoldager@sund.ku.dk