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Rare Mutation Provides “Protective Genetic Superpower” Against Obesity

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  1. The Good Doctor

    The Good Doctor Golden Member

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    Scientists have discovered a rare gene variant that appears to act like a “protective genetic superpower” against weight gain.

    As reported in the journal Science, researchers from the Regeneron Genetics Center, Duke University Medical Center, and a number of universities have discovered that people with genetic mutations in the GPR75 gene have a 54 percent reduced risk of obesity.

    For the first part of the study, the researchers analyzed genetic and health data from 645,000 volunteers from the UK, the US, and Mexico. Individuals who have at least one inactive copy of the GPR75 gene, which has become inactivated through “loss of function” mutations, tended to weigh about 5.4 kilograms (12 pounds) less, had a lower Body Mass Index (BMI), and face a 54 percent lower risk of obesity than those without the mutation.

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    However, the protective mutations were relatively rare, appearing in about one of every 3,000 people sequenced.

    This initial finding was later backed up by another experiment using mice that had been genetically engineered to lack copies of the GPR75 gene. These genetically tweaked mice gained 44 percent less weight than mice without the mutation when both groups were fed a high-fat diet.

    While behavioral and environmental factors play a role in obesity, it’s well-established to have a link to genetics. Since genetic factors play an important role in metabolism, as well as how people acquire energy and store it as fat, it’s apparent that certain genes will influence the risk of developing obesity. No single gene is to blame, however. Previous studies have identified hundreds of loci in the genome that appear to be connected with obesity and the way they influence the risk of obesity is likely to be deeply complex.

    Obesity continues to be one of the biggest challenges in global health. Worldwide obesity has nearly tripled since 1975. As of 2016, more than 1.9 billion adults were overweight, of these, over 650 million were obese, according to the World Health Organization.

    Not least could this discovery provide new insights into the genetic basis of obesity, but it could someday help to address the global epidemic of obesity.

    "Discovering protective genetic superpowers, such as in GPR75, provides hope in combating global health challenges as complex and prevalent as obesity," George D. Yancopoulos, President and Chief Scientific Officer at Regeneron who was part of the study, said in a statement.

    "Discovery of protective mutations… will allow us to unlock the full potential of genetic medicine by instructing on where to deploy cutting-edge approaches like gene-editing, gene-silencing and viral vector technologies."

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