Obesity Gene Affects One In Ten People

April 15, 2006

http://www.medicalnewstoday.com/healthnews.php?newsid=41672

Main Category: Obesity/Overweight/Fitness NewsArticle 14 Apr 2006 - 8:00am (PDT)A recent discovery may have a genetic explanation why some people are obese while others are not. According to scientists from Genetics and Genomics, Boston University Medical School, about 10% of humans have a sequence variation close to the INSIG2 gene. You can read about this discovery in the journal Science (April 14). Michael Christman, lead researcher in this study, said that this discovery helps us understand why some people are obese, but for the moment, it does not help us get anywhere nearer a genetic treatment for obesity. One day, perhaps. INSIG2 is a gene that controls insulin - in fact, it is induced by insulin. It inhibits the synthesis (manufacturing in the body) of fatty acid and cholesterol. People with a sequence variation near the gene seem less able to inhibit the synthesis of fatty acid and cholesterol - in other words, these people tend to accumulate more fat in the body (they get fat more easily). Scientists have long believed that a good percentage of obese people are so because of their genes. This is the first study to identify a genetic factor in obesity. This news should come as a great relief to millions of obese people around the world, who for years have been puzzled and distressed at their never-ending war against flab - and wondering why they find it so hard. Perhaps being fat, for many people, is more to do with the way you were born, rather than with the way you conduct your life. Christman added that although we have no idea how this may offer treatment today, it will be useful as a first step towards finding effective treatment one day. Once the molecular pathways of obesity are understood, he said, we will be nearer to effective treatment for obesity. Obesity is becoming more and more prevalent in most parts of the world. Some say it is due to our eating habits, others say it is more to do with doing less exercise than we used to. The Atkins bunch tell us to eat fewer carbohydrates and blame the low fat bunch for the obesity spread, another association says we should eat less fat saying the Atkins bunch are just in it for the money, others say it is all down to ‘food combining'. What all these ‘gurus' have in common is that they have made absolutely no difference to the speed at which obesity is spreading around the world - especially during the last ten years when all these ‘breakthrough diets' appeared. Fifty years ago people in the USA and UK used to consume, on average, more calories per day than we do today, but they were thinner - we know they were more physically active. Written by: Christian NordqvistEditor: Medical News Today

http://abcnews.go.com/Health/print?id=1839156

Scientists Narrow in on Genetic Cause of Obesity

Long-Term Study Shows 10 Percent of Population May Have Gene

By DR. JENNIFER CAUDLE

April 13, 2006 — - It's no secret that a combination of greasy fast food and couch potatolike behavior has contributed to America's obesity epidemic.

Many scientists, however, have also wondered whether something else is involved: Could there also be a genetic explanation?

Research is showing this may indeed be the case for some people. In today's issue of the journal Science, researchers explain how they have found a variation, or "misspelling," of DNA located near a gene that normally affects fat metabolism.

"It's the first common genetic variant to be associated with obesity," said Dr. Michael Christman, a lead researcher and chair of the Department for Genetics and Genomics at Boston University.

DNA contains genetic material, or instructions, for cells throughout the body. Genes are pieces of DNA that carry out these instructions.

Researchers discovered this variation after analyzing DNA samples collected from 9,881 people over a 24-year span. They also discovered that people of different racial, ethnic and age groups who had the same misspelling had an increased risk of obesity.

"The strength of this study was that we were able to replicate the data in different populations," said Dr. Alan Herbert, a lead researcher of the study and assistant professor of genetics and genomics at Boston University.

Ten percent of the population has this misspelled DNA, scientists estimate, and those who have it also have a 30 percent to 50 percent increased risk of becoming obese.

Obesity is considered a risk factor for a number of diseases such as hypertension, diabetes and stroke. In recent years, obesity rates have increased drastically in both adults and children.

The study could lead to a better understanding of what role genetics plays in obesity.

"We have not understood what the common genes are that predispose us to the disease," Christman said.

Another Piece in the Puzzle

Genetic researcher Dr. Teri Manolio, of the National Human Genome Research Institute, said the study was one of the best she'd seen on the topic.

"It followed people for so long and so carefully … studied family associations but also studied unrelated people. … The results weren't a fluke," Manolio said. The researchers hope that the findings will have an impact on other scientific research and on how pharmaceutical companies design drugs.

"It's like finding another piece in the puzzle. … Eventually we'll see the whole picture," said Nan Laird, a co-author of the study and professor of biostatics at the Harvard School of Public Health.

Even with more research, scientists caution about relying solely on genetics to explain a few extra pounds.

"It's not for us to think, 'Obesity is in your genes -- there's nothing you can do about it,'" Manolio said.

"We need to pay more attention to increasing physical activity and moderating dietary intake," she said.

Dr. Jennifer Caudle is an intern at Delaware County Memorial Hospital in Drexel Hill, Pa. Caudle plans to specialize in family practice.

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http://www.forbes.com/forbeslife/health/feeds/hscout/2006/04/13/hscout532106.html

Genetic Variant Increases Risk of Obesity04.13.06, 12:00 AM ET

THURSDAY, April 13 (HealthDay News) -- Scientists say they've identified a genetic quirk that leads to obesity, and they add that more genetic variants are waiting to be reported.

There's no immediate practical application of the finding, said Michael F. Christman, chairman of genetics and genomics at Boston University Medical School, and a member of the team reporting the discovery in the April 14 issue of Science. But it could someday lead to more effective anti-obesity drugs, he noted.

About half the risk of obesity is determined by the genes people carry, and half of that risk is determined by eight to 10 genes, Christman said. So, the just identified genetic variant, which sits on chromosome 2, is associated with about 5 percent of obesity, he said.

The variant is present in about 10 percent of people around the world, the researchers reported. It is physically close to a gene designated INSIG2, which is involved in fat metabolism. That location suggests it could influence the functioning of the INSIG2 gene, which produces a protein that inhibits production of fatty acid and cholesterol, the researchers said. But more work is needed to say exactly how the relationship between the genes works.

The discovery was made by applying data from the Human Genome Project to people in the long-running Framingham Heart Study and then verifying the relationship in other groups of people around the world, Christman said.

"What we did was to look at 116,000 different points across the human genome where people vary in their sequence," he said. "You know, our genomes are 99.9 percent the same, and it's that one-tenth of 1 percent that makes us different."

Since details on obesity are collected in the Framingham study, the researchers were able to relate this one genetic variant to a propensity for overweight. "Further work showed the same association with obesity in populations all around the world, Europeans, Africans and children," Christman said.

The study has detected other genetic variants associated with obesity in Framingham participants, and they are being checked to see if there is the same association in other groups of people, he said.

"We think the other nine or so genes will be found very soon," Christman said. "Others are doing the same thing. Ours is one of the first, but there will be a flood of these over the next several years."

How will the information gathered in these studies be used? Not in way many people might assume -- genetic testing to determine susceptibility to obesity, Christman said. Rather, it will be used to identify molecular processes in the human body that make people fat, he said.

Once the molecular pathways of obesity are known, researchers could use that knowledge to develop drugs targeting the pathways, Christman said. That could drive down the cost of drug development and result in better drugs, he said.

The discovery was made in a collaboration involving institutions in the United States and Europe. Researchers at the Harvard School of Public Health developed statistical methods used in the analysis, and studies in other populations were done by researchers in Germany and at Loyola University in Chicago, among others.

More information

For more on the role of genetics in obesity, visit the American Obesity Association.