Does FTO have a paradoxical effect in fetal life?

BACKGROUND: Low weight at birth is associated with obesity in later life. One hypothesis to explain such an association is that genetic variants that increase the risk of obesity also reduce fetal weight. Recently, obesity in adults was found to be associated with common variants of the fat mass and obesity-associated (FTO) gene. We examined the association between FTO polymorphisms and birth weight in a singleton, full-term birth cohort of 494 newborn-mother pairs without any complications. RESULTS: The risk alleles for obesity (“A” allele for the rs9939609 FTO variant and “G” allele for the rs9930506 FTO variant) were associated with low weight at birth. The mean differences per risk allele were −79 g (95% CI: −129 to −30; p = 0.002) for rs9939609 and −84 g (95% CI: −131 to −36; P < 0.001) for rs9930506. The level of association remained statistically significant after adjustment for the maternal risk allele and for variables usually associated with birth weight (−50 g, 95% CI: −99 to 0; p = 0.05 for rs9939609 and −48 g, 95% CI: −100 to 0; p = 0.05 for rs9930506). In the follow-up, the allelic difference in weight was attenuated over time. CONCLUSIONS: The FTO variants that confer a predisposition to obesity later in life appear to be associated with low weight at birth. This finding favors the hypothesis of a common genetic denominator that predisposes to a low weight at birth and obesity in adults.