Not surprisingly, there has been intense interest in the genetics of obesity in recent years. Obesity is a major health problem, resulting in tens of thousands of premature deaths and billions of dollars in healthcare costs each year in the United States, and it is known from twin and family studies that weight is a highly heritable trait.
The genetic mutations and variations identified so far explain only a small percentage of the variability in body mass seen in the population. Some exciting clues have been found, however, as to why some people are more prone to obesity than others and how this might be counteracted. But new research, published online this week in the American Journal of Human Genetics, shows that caution must be taken in moving from genetic discoveries to drug development.
Variations in the FTO gene have consistently been associated with obesity. On average, people who carry two copies of the “risky” version of this gene weigh six to eight pounds more than those who carry none. Mice completely lacking the FTO gene were shown to be leaner than their normal littermates, despite being less active. These results have led some to suggest that inhibiting the FTO protein with a drug could be a good for obesity treatment or prevention.
(23andMe customers can see their FTO data in the Obesity Research Report.)
But an international team of researchers led by Sarah Boissel of the Université Paris Descartes in France has found that a mutation that interferes with the function of the FTO protein is associated with a lethal genetic condition. Members of a large, inbred Palestinian family born with two copies of this mutation had multiple developmental abnormalities and died before the age of three. Based on their results, Boissel and her colleagues warn that any research exploring the use of FTO inhibitors as obesity treatments must include a “careful assessment” of the potential to cause birth defects and other toxic side effects.
More about FTO:
SNPwatch: Gene Variant Linked to Obesity Affects Food Choices in Children