A genetic change that makes white people feel famished has been found

The common DNA mutation was found in people of European ancestry and the find reveals that a minor change can have a significant impact on the production of several hormones controlling our appetite, which scientists say is "definite evidence that common obesity is a disease of the appetite and satiety." The mutation, each copy of which raises the risk of obesity by 50%, is found in around one person in every four white people, according to research published in Nature Genetics by an international team led by Imperial College London. Understanding this mechanism will help scientists to develop new treatments, notably by making obese people feel full. The gene, called PCSK1, is the recipe for the body to make the "proconvertase enzyme", which is responsible for producing fully functioning versions of hormones such as insulin, glugagon and melanocortin. These are all involved in controlling the rate of metabolism. Changes in the PCSK1 gene cause relatively minor abnormalities in the enzyme that can have a major effect on the way the body responds to the hormones, which all play a major role in regulating weight. The discovery was made by Prof Phillipe Froguel of Imperial with colleagues there and in France, Denmark, Sweden and Germany, after screening the genetic makeup of over 13,000 people. They discovered a significant association between the genetic mutation in PCSK1 and a tendency to develop obesity. These variants were also associated increased risk of childhood obesity. "This is the first time that we have found a strong link between common mutations and common obesity in the PCSK1 gene," says Professor Froguel. "We know that common forms of obesity depend on variations in multiple genes, so this is an important addition to the list of genes we need to consider as therapeutic targets for treatment in the future." Many genes have now been linked to obesity including MC4R reported by Prof Froguel’s team in March 2008 and FTO, reported by the same team and independently by an Oxford group.