Lean gene and heart disease risk

By Dr. Ananya Mandal, MDJun 27 2011

According to a new study published Sunday, being lean may not always lead to a lower risk of heart disease and diabetes. The researchers have successfully identified a gene linked both to having a lean body and to a higher risk of metabolic diseases.

The study comes from Britain's Medical Research Council Epidemiology Unit where the researchers say that while a so-called “lean gene” was linked to having less body fat, it was also linked to an increased risk of heart disease and type 2 diabetes - illnesses normally associated with being overweight.

Ruth Loos, whose study was published in Nature Genetics journal said, “We've uncovered a truly fascinating genetic story, and when we found the effect of this gene, we were very intrigued.” The team examined the genetic code of more than 75,000 people to look for the genes that determine body fat percentage, and found strong evidence that a gene called IRS1 is linked with having less body fat. They also found that IRS1 leads to having unhealthy levels of cholesterol and glucose in blood - key markers for so-called metabolic diseases like heart disease and diabetes.

They found the gene was only linked to lower levels of fat under the skin, called subcutaneous fat, but not to the more harmful fat that surrounds the organs, called visceral fat. Dr. Loos said this study shows that people with the IRS1 gene are less able to store subcutaneous fat, and may therefore store fat in other parts of the body where it might pose more risk to organ function. She suggested that the effects may be more pronounced in men because they store less fat than women, and could be more sensitive to changes in its distribution.

She warned that this study does not change anything for most people and said, “People who are lean are generally healthier than people who are overweight or obese. But we all know some people who are lean and also may have high cholesterol or have a heart attack before the age of 50 - so maybe this gene is one factor in looking healthy but still being at risk for cardiovascular disease and type 2 diabetes.” She said that current advice to modify lifestyle factors like diet, exercise, cutting out smoking and maintaining a healthy weight also play a vital role in reducing the risk.

Professor Nick Wareham, the unit’s director, added, “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.” Professor Jeremy Pearson, of the British Heart Foundation, said, “These results reinforce the idea that it is not just how fat you  are, but where you lay down fat that’s particularly important for heart risk. Fat stored internally is worse for you than fat stored under the skin.” Professor Douglas Kiel, from Harvard Medical School in Boston, US, added, “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.”

Heart disease is the world's biggest killer, claiming 17.1 million lives a year, according to the World Health Organization. Experts say a global epidemic of obesity is threatening to cause a wave of heart disease and type 2 diabetes.