Rogue gene behind multiple heart disease risks identified

In a major breakthrough, researchers have identified a key gene, mutation of which could lead to a cluster of disorders such as obesity, high blood pressure and diabetes - together know as metabolic syndrome.

Having any or combinations of these factors could significantly increase risks of heart diseases and strokes.

The mutation was in the gene 'Dyrk1B' - an enzyme that in normal conditions regulates the balance of muscle to fat as well as stable glucose levels by controlling the signaling pathways.

When mutated, 'Dyrk1B' inhibited pathways that keep glucose levels stable, and become hyperactive to promote the production of fat on the body, the researchers found.


“The entire pathway of this gene seems to be linked with glucose and fat metabolism, through the differentiation of stem cells into muscle, bone, cartilage, and fat tissue,” said Arya Mani, an associate professor of cardiology and genetics at Yale School of medicine.

“Our findings suggest that mutation in genes that regulate the fate of these cells can result in more fat instead of muscle,” Mani added.

The study involved three large families with familial, or inherited central obesity, early-onset coronary artery disease, hypertension, and diabetes.

Using whole-exome sequencing, they identified the so-called “founder mutation” - a genetic abnormality that begins in one ancestor and repeats through successive generations of a family.
The researchers found that mutation of Dyrk1B was present in all family members affected by metabolic syndrome, and absent in those who were unaffected.

Researchers hope that it would be possible to develop therapies that can eliminate the impact of Dyrk1B mutation.

“The advantage of Dyrk1B as an obesity gene is that its inhibition may not only reduce body weight, but favourably affect other risk factors,” said Ali Keramati, resident in internal medicine at Yale School of Medicine.

The study appeared in New England Journal of Medicine.

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