27th June 2011
‘Lean Gene’ Increases Risk of Heart Disease and Diabetes
Having a leaner body may not always give you a lower risk of heart disease and diabetes, according to the newest findings of a Medical Research Council (MRC) study. Researchers led by the MRC Epidemiology Unit have identified a gene that is linked with both having less body fat and an increased risk of metabolic diseases such as type 2 diabetes and heart disease.
By examining the genetic code of over 75,000 people to look for the genes that determine body fat percentage, the research team found strong evidence that the gene IRS1 is linked with having less body fat. On further investigation, they found that this gene also leads to having unhealthy levels of cholesterol and glucose in blood, which are key markers for metabolic diseases.
To try to understand why a gene linked with being lean carried an increased risk of metabolic disease, the scientists looked at body fat distribution in people carrying the gene. They found that the gene lowers only the fat under the skin, called ‘subcutaneous’ fat, but not the more harmful fat that surrounds the organs called ‘visceral’ fat. The authors speculate that people with this gene variant are less able to store subcutaneous fat, and may therefore store fat elsewhere in the body where it may interfere with normal organ function. The researchers found these observations were more pronounced in men than in women.
Dr Ruth Loos, the lead scientist on the project from the MRC Epidemiology Unit, said:
“We’ve uncovered a truly fascinating genetic story and when we found the effect of this gene we were very intrigued by the unexpected finding. People, particularly men, with a specific form of the gene are more likely to be lean and to develop heart disease and type 2 diabetes. In simple terms, it is not only overweight individuals who can be predisposed for these metabolic diseases, and lean individuals shouldn’t make assumptions that they are healthy based on their appearance.
“What we’ve discovered is that certain genetic variants keep you lean by reducing how much fat you store under your skin. We don’t know for sure, but we can speculate that these individuals are then more predisposed to store fat elsewhere, such as in the liver and in muscle. The effect may be more pronounced in men due to the different body fat distributions between the sexes. Men store less fat than women, so they are more sensitive to changes in its distribution.
“Although our genetic make-up can help to determine whether we’re predisposed to certain diseases, we mustn’t forget that what we eat and how active we are also plays a vital role in maintaining good health.”
The research consortium used data from 26 different genetic studies and involved scientists at 72 institutions in 10 countries.
Professor Nick Wareham, director of the MRC Epidemiology Unit, said:
“This is fantastic example of the MRC’s expertise in international collaborative research. The research will provide new insights into why not all lean people are healthy and, conversely, why not all overweight people are at risk of metabolic diseases. A better understanding of the links between body fat and risk of disease will help to develop more targeted treatments for these diseases, alongside recommended lifestyle changes.”
The research is reported in the journal Nature Genetics.