Female body shape gene may increase risk of type 2 diabetes

April 10, 2018, University of Oxford
Female body shape gene may increase risk of type 2 diabetes. Credit: Shutterstock

Scientists at the University of Oxford have identified a gene that in women is linked to the creation and location of new fat cells and in turn contributes to an increased risk of type 2 diabetes.

Published in Nature Genetics, the paper examined the effect of a gene called KLF14. The researchers found that genetic variations that control KLF14 have little impact on overall weight but they have a marked impact on where in the body any is stored. In women, versions of the gene that are result in fat being preferentially deposited around the hips, rather than around the abdomen, provide protection against .

The different variations of KLF14 have an impact on the development of fat , and a striking effect on their size. In women carrying the version of the KLF14 gene that is associated with increased risk of diabetes, the individual fat cells are much larger and full of fat. This is likely to because there are fewer such cells in the first place, such that each cell ends up needing to take up more fat. This is known to result in inefficient, unhealthy that are more likely to contribute to diabetes.

The study, which was an international collaboration with King's College London, MRC Harwell, the University of California in Los Angeles, University of Pennsylvania and others, also showed that the effects of these were specific to females. Not only that, only those versions of the gene inherited from an individual's mother are active. In women who inherited the risk version of the gene from their mothers, the impact is to increase diabetes risk about 30%.

The findings provide new insights into some of the mechanisms involved in the development of diabetes, and demonstrates that abnormalities in , as well as those in liver and in the insulin-producing cells of the pancreas can contribute. It is anticipated that this understanding may lead to better ways of treating and preventing diabetes in the future.

Dr. Kerrin Small, one of the lead authors of the study from the Department of Twin Research and Genetic Epidemiology said: "These findings provide one of the most complete understandings of a piece of genetic data – we have studied the KLF14 gene to the point that we understand not only where and how it acts in the body but also who it acts in.

"We hope that by building on these findings with further research to try and understand why the gene variant only affects diabetes risk in women that we can contribute towards better treatment plans and prevention and move towards more personalised approaches to medicine."

Professor Mark McCarthy, another lead author, from the University of Oxford said: "Being overweight is known to increase the risk of type 2 diabetes, but this study shows that not all fat is equal: where any excess fat is stored in the body has a big impact on disease risk. Here we identify a key gene involved in in determining whether excess fat is stored around the hips (where it tends to be free of metabolic consequences) or around the waist (where it is particularly likely to increase ).

"Rather that assuming that genetic variations exert their effects in the same way in different people, our new work highlights the importance of taking a 'holistic' approach to understanding the causes of disease, interrogating how function in different tissues and in different sexes."

Explore further: Genetic variant shown to influence women's body shape and diabetes risk

More information: Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition, Nature Genetics (2018). nature.com/articles/doi:10.1038/s41588-018-0088-x

Related Stories

Genetic variant shown to influence women's body shape and diabetes risk

October 11, 2015
A genetic variant near the KLF14 gene regulates hundreds of genes that govern how and where women's bodies store fat, which affects their risk of developing Type 2 diabetes, according to research presented at the American ...

Researchers discover 'master switch' gene for obesity, diabetes

May 15, 2011
A team of researchers, led by King's College London and the University of Oxford, have found that a gene linked to type 2 diabetes and cholesterol levels is in fact a 'master regulator' gene, which controls the behaviour ...

Diabetes gene found that causes low and high blood sugar levels in the same family

January 15, 2018
A study of families with rare blood sugar conditions has revealed a new gene thought to be critical in the regulation of insulin, the key hormone in diabetes.

Ten new diabetes gene links offer picture of biology underlying disease

August 12, 2012
(Medical Xpress) -- Ten more DNA regions linked to type 2 diabetes have been discovered by an international team of researchers, bringing the total to over 60.

Non-coding DNA implicated in type 2 diabetes

January 12, 2014
Variations in non-coding sections of the genome might be important contributors to type 2 diabetes risk, according to a new study.

Using human genetics to reveal fundamental processes involved in type 2 diabetes

November 9, 2015
Researchers at Oxford and Liverpool universities have identified genetic markers that could be used to understand people's risk of developing type 2 diabetes. Their work is published in Nature Genetics today.

Recommended for you

Analytical tool predicts genes that can cause disease by producing altered proteins

July 19, 2018
Predicting genes that can cause disease due to the production of truncated or altered proteins that take on a new or different function, rather than those that lose their function, is now possible thanks to an international ...

Childhood stress leaves lasting mark on genes

July 18, 2018
Kids who experience severe stress are more likely to develop a host of physical and mental health problems by the time they reach adulthood, including anxiety, depression and mood disorders. But how does early life stress ...

Study shows DNA methylation related to liver disease among obese patients

July 18, 2018
DNA methylation is a molecular process that helps enable our bodies to repair themselves, fight infection, get rid of environmental toxins, and even to think. But sometimes this process goes awry.

Protein found to be key component in irregularly excited brain cells

July 17, 2018
In a new study in mice, researchers have identified a key protein involved in the irregular brain cell activity seen in autism spectrum disorders and epilepsy. The protein, p53, is well-known in cancer biology as a tumor ...

World's largest study on allergic rhinitis reveals new risk genes

July 17, 2018
An international team of scientists led by Helmholtz Zentrum München and University of Copenhagen has presented the largest study so far on allergic rhinitis in the journal Nature Genetics. The data of nearly 900,000 participants ...

New platform poised to be next generation of genetic medicines

July 16, 2018
A City of Hope scientist has discovered a gene-editing technology that could efficiently and accurately correct the genetic defects that underlie certain diseases, positioning the new tool as the basis for the next generation ...

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.