What are clinical implications of genetic testing for the FTO (fat mass and obesity) gene?

Updated: Feb 10, 2016
  • Author: Ali Torkamani, PhD; Chief Editor: Keith K Vaux, MD  more...
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Before any clinical applications for genetic testing for FTO variants can be considered, the mechanistic link between FTO and obesity needs to be further clarified. One study showed that a loss-of-function FTO mutation in humans led to postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits, facial dysmorphism, and early lethality, [25] indicating that pharmacologic inhibition of FTO in an attempt to combat a predisposition to obesity could yield multiple adverse reactions.

Moreover, a clear link between FTO demethylase activity and obesity has yet to be made. It is possible that FTO plays a specialized role in the hypothalamus, perhaps as a transcriptional regulator, and mediates obesity in a manner independent of its catalytic activity, in which case pharmacologic inhibition would not be useful. On the other hand, it is also possible that the true in vivo effect of FTO has yet to be described.

The association of FTO variants with obesity certainly hints at a novel pathway to obesity and suggests ways in which genetic testing for FTO variants might play a role in potential clinical interventions down the road.

In the meantime, since diet and lifestyle changes seem to blunt the effects of a genetic predisposition toward obesity due to the presence of an FTO risk allele, [26] there may be a more immediate role for genetic testing in the clinic; such testing may provide a means of encouraging allele carriers to implement diet and lifestyle changes that discourage obesity and improve their overall health.

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