Researchers identify gene that causes obesity-related metabolic syndrome

May 15, 2014 by Helen Dodson, Yale University
Researchers identify gene that causes obesity-related metabolic syndrome

(Medical Xpress)—Yale-led research has identified a genetic mutation responsible for the cluster of cardiovascular risk factors that comprise the obesity-related "metabolic syndrome." The study appears in the May 15 issue of the New England Journal of Medicine.

Until now, genetic analysis has been successful in identifying mutations that predispose people to individual . Success has been more limited, however, in mapping mutations responsible for the constellation of disorders that include obesity, , and elevated that, when combined, greatly increase the risk of cardiovascular disease, heart failure, and diabetes. Together, these conditions are known as metabolic syndrome.

The researchers studied three large families with familial, or inherited central obesity, early-onset coronary artery disease, hypertension, and diabetes. Using whole-exome sequencing, they identified a so-called "founder mutation"—a genetic abnormality that begins in one ancestor and repeats through successive generations of a family.

The mutation was in the gene Dyrk1B, an enzyme that regulates the balance of muscle to fat as well as stable glucose levels by controlling the signaling pathways. When mutated, the researchers found, Dyrk1B inhibited pathways that keep stable, and "turned on" the pathways that promote the production of fat on the body.

The mutation was present in all family members affected by , and absent in those who were unaffected.

The researchers believe this mutated gene is the likely reason why patients with it have reduced muscle mass but increased fat mass, even at a very young age. "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 senior author Dr. Arya Mani, associate professor of cardiology and genetics and member of the Yale Cardiovascular Research Center. "Our findings suggest that mutation in genes that regulate the fate of these cells can result in more fat instead of muscle."

Mani adds that animal studies suggest the activation of genes like Dyrk1B may actually increase appetite and cause weight gain. Therefore, he notes, because the gene is a protein kinase, which modifies other proteins, it may be an excellent target for potential therapies that restore balance and reduce or eliminate the impact of the genetic mutation.

"The advantage of Dyrk1B as an obesity gene is that its inhibition may not only reduce body weight, but favorably affect other risk factors," adds first author Dr. Ali Keramati, resident in internal medicine at Yale School of Medicine.

Explore further: Breast cancer gene protects against obesity, diabetes

Related Stories

Breast cancer gene protects against obesity, diabetes

March 12, 2014
(Medical Xpress)—The gene known to be associated with breast cancer susceptibility, BRCA 1, plays a critical role in the normal metabolic function of skeletal muscle, according to a new study led by University of Maryland ...

Mutation leads to combined hyperlipidemia; genetic targeting may reverse it

February 5, 2014
(Medical Xpress)—A Yale study has identified the underlying genetic basis of combined hyperlipidemia, as well as a treatment that may normalize the condition. The study appears in Cell Metabolism.

Obesity can amplify bone and muscle loss, researchers say

April 16, 2014
Florida State University researchers have identified a new syndrome called "osteosarcopenic obesity" that links the deterioration of bone density and muscle mass with obesity.

Rethinking genetic links to obesity: IRX3 is likely the 'fat gene'

March 12, 2014
Mutations within the gene FTO have been implicated as the strongest genetic determinant of obesity risk in humans, but the mechanism behind this link remained unknown. Now, an international team of scientists has discovered ...

Key genetic mutations could be new hope for adrenocortical tumor patients

April 4, 2014
Chinese researchers from Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, BGI, and other institutions have discovered that the activating hotspot L205R mutation in PRKACA gene was closely associated with ...

Linking vascular inflammation to obesity and atherosclerosis

May 6, 2014
A study in The Journal of Experimental Medicine shows that IκB kinase β (IKKβ) functions in smooth muscle cells to regulate vascular inflammatory responses and atherosclerosis development.

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.