Tendency toward obesity tied to genes, large study shows

Genetic therapy years off

diet, exercise still important, scientists add

April 13, 2007|By Dennis O'Brien | Dennis O'Brien,Sun Reporter

Ever wonder why some people can eat anything they want without gaining weight, while others fight a year round battle of the bulge?

British researchers confirmed yesterday what many weight-watchers and scientists have long suspected: There are obesity genes that can add inches to your waistline.

A team of scientists examined the DNA of 40,000 people and found that variations in a specific gene sequence increased the likelihood of being overweight.

Those with two copies of the variant gene sequence known as FTO were nearly seven pounds heavier than those without it. They also were 70 percent more likely to be obese, the researchers found.

That doesn't mean weight-watchers should give up. Scientists say a healthy diet and regular exercise are still important - and the specific causes of weight gain vary from one person to the next.

But the study shows there's another reason why some of us are more likely to put on pounds than others. "What we're suggesting is genetics plays a role, as well as lifestyle," said Dr. Andrew Hattersley, a researcher at Peninsula Medical School in Exeter, England, and a senior author of the report in today's issue of the journal Science.

The DNA analysis was limited to white European adults and children, but researchers believe the findings apply to other nationalities and ethnic groups. They're planning future studies to find out for sure.

Despite their increasing knowledge, scientists say genetic therapies for obesity are still years away. They need to identify additional genes that play a role in obesity, and until then, healthy living remains the best advice.

"It would be wrong to say that a single gene like this is something that, because of its effect, would be something we would want to translate into a genetic test," said Dr. Mark McCarthy, a co-author from Oxford University. "Lifestyle interventions, eating less and exercising more remain the mainstay of effective therapy."

Researchers don't know how the FTO gene sequence works. "I can't give you a pat answer as to how this influences weight," McCarthy said. Future studies will show whether it regulates appetite or metabolism, or has some other effect.

What makes this study important is the scope of its findings, observers say. "Other genes have been linked to obesity, but they haven't been replicated in such large population groups," said Dr. Soren Snitker, who studies the genetics of obesity and diabetes at the University of Maryland School of Medicine.

Last year, for example, researchers at Boston University found that variations of a gene that regulates fatty acids, known as Insig2, can signal a predisposition to obesity in about 10 percent of European and African-American populations.

But the latest British findings represent the first genetic fingerprint linked to obesity in a large group: More than half the population had at least one copy of it.

Still, scientists have been debating the role of genetics in obesity for years, and the study's authors say their report won't end those arguments.

"It's difficult to come up with accurate measures of how much of it is genetic and how much is environmental," said Timothy Frayling, the lead author and a Peninsula Medical School researcher.

Scientists have found that twins raised separately experience the same weight gain patterns, and that adopted children gain weight in ways that more closely resemble their biological parents than their adoptive ones, added UM's Snitker.

But the turning point in the debate over behavior vs. nature came in the mid-1990s, when mice with genetic deficiencies that inhibited their production of the hormone leptin were three times heavier than normal mice, Snitker said. Leptin inhibits food intake and stimulates energy production.

"Everybody believed up till then that obesity was a moral weakness, that people just had to pull themselves together," Snitker said. "We know now that isn't the case."

The findings announced yesterday were discovered by researchers initially looking at Type 2 diabetes in a broader effort to identify the genetic underpinnings of numerous diseases. They initially compared DNA from 2,000 people who had Type 2 diabetes with DNA from 3,000 people without it.

They found that the FTO variant was more common among diabetics. But their results also showed the variant plays a role in weight patterns, so they probed deeper, examining the DNA from another 35,000 people participating in 13 different health studies in England, Finland and Italy.

Meanwhile, obesity will remain a major concern among health experts. An estimated one-third of adults in the U.S. are obese, and up to two-thirds are overweight, according to the Centers for Disease Control and Prevention. An estimated 16 percent of children and adolescents between 6 and 19 are overweight, the CDC says.


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