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Fat Gene: It Really Exists

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Fat Gene: It Really Exists

But Magic Bullet Weight-Loss Pill Still Years Away

By Jeanie Davis

Reviewed By Michael Smith, MD

WebMD Medical News

Oct. 30, 2002 -- Finally, there's proof -- those love handles and saddle bags may not be your fault. Researchers have identified a gene that directly causes obesity. They've christened it HOB1, for Human Obesity 1.

"It's very clear that obesity is [inheritable]," says Steven Stone, PhD, senior scientist at Myriad Genetics Inc. "This is the very first example of a gene that is involved in that process in humans."

In fact, the HOB1 discovery is likely the first baby step to the ultimate weight-loss pill -- one that could benefit those who are severely overweight, Stone tells WebMD. "It's not unreasonable that people who are less obese could get some benefit, too."

Researchers have long told us that the propensity for weight gain lies in our genes. Studies of twins and families have provided ample evidence of this. But until now, scientists have not isolated the gene or genes involved in that vulnerability.

"Obesity carries a social stigma," Stone tells WebMD. "But here is more evidence that it is a medical condition, not always a case of overindulgence."

In their study, Stone and colleagues focused on thousands of Utah families, all with two or more close relatives (siblings, parents, or children) who were more than 100 pounds overweight.

Through a complex process, the researchers discovered a region of the human DNA that contained highly significant evidence for a gene that predisposed to obesity, writes Stone in his report, published in the April 15 issue of the American Journal of Human Genetics.

In fact, the same gene may be linked with diabetes, too, he tells WebMD. Shortly after his discovery, another research group at Myriad "discovered" the same gene when investigating genetic causes of diabetes. The researchers think the gene may be involved in diabetes, but there is no evidence that it's a direct cause.

Curiously, the gene was strongly linked with women in the study group, Stone says. It could be that the gene may have an effect on men, but one that's simply weaker than in women.

Unfortunately, obesity is more complex than one little gene, Stone says. Coming up with that ultimate diet pill is going to take a lot more research.

HOB1 is a very significant contributor to the disease, but it's not the only gene involved, he tells WebMD. "Obviously, the goal of this work is to identify genes involved in predisposition then initiate a drug discovery. If you identify the genes involved, then you can try to modulate the activity with molecules as a way of treating the disease. That's our goal."

It's taken his group six years to isolate HOB1, he says. "The whole process can take 12 years on average, unless you get lucky."

For some perspective, WebMD turned to Aubrey Milunsky, MD, director of the human genetics center at Boston University School of Medicine.

Milunsky is author of the book Your Genetic Destiny: Know Your Genes, Secure Your Health, Save Your Life.

When news broke last year about the discovery of leptin (a protein directly linked with obesity), "it was a big finding, but it applied to 1% of people who were morbidly obese," Milunsky tells WebMD. "There was a lot of initial hype, but then we finally saw the reality that leptin accounts for obesity in the very occasional person, not the average overweight individual."

HOB1 could likely be the same scenario, he says. "It's been discovered in a very select set of families -- and particularly confined to females. That's kind of curious. It means there are other factors at work in concert with the gene."

The study of such complex disorders -- that result from the interaction of a handful of genes and some environmental factors -- is moving along at breakneck speed, Milunsky tells WebMD. "The general purpose [of this research] is undoubtedly financial."

Case in point: "If one was able to recognize at birth whether little Johnny was susceptible to high blood pressure, diabetes, obesity, heart disease, and so on, there might be ... medications that could intercede and change all that. There could be medications taken once daily that would prevent them."

Don't look for that ultimate magic "obesity bullet" any time soon, Milunsky says. "The public in general is spending millions on diet books, methods for weight loss. But it's complex territory that is not going be solved easily. We're a long way from an 'obesity pill.' You can't suppress appetite in very simple ways until you know precisely what the trigger is."

In the meantime: "Watch your calories and exercise and don't spend money on diet books," says Milunsky.

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