FTO genotype, vitamin D status, and weight gain during childhood

Abstract

Previous evidence suggests that variants in the fat mass and obesity-associated gene (FTO) affect adiposity in an age-dependent fashion in children, and nutritional factors may modify genotype effects. We assessed the effect of FTO rs9939609 on BMI and BMI-for-age Z score changes during childhood in a population-based longitudinal study in the Brazilian Amazon and investigated whether these effects were modified by vitamin D status, an important nutritional factor related to adiposity. At baseline, 1,088 children aged <10 years had complete genotypic and anthropometric data; 796 were followed up over a median 4.6 years. Baseline vitamin D insufficiency was defined as <75 nmol/L. We observed a 0.07 kg/m(2)/year increase in BMI and a 0.03 Z/year increase in BMI-for-age Z score per rs9939609 risk allele over follow-up (P = 0.01). Vitamin D status significantly modified FTO effects (P for interaction = 0.02). The rs9939609 risk allele was associated with a 0.05 Z/year increase in BMI-for-age Z score among vitamin D-insufficient children (P = 0.003), while no significant genetic effects were observed among vitamin D-sufficient children. Our data suggest that FTO rs9939609 affects child weight gain, and genotype effects are more pronounced among children with insufficient vitamin D levels.

Figure 1

Mean BMI among urban Amazonian children according to FTO rs9939609 genotype at each study assessment (2007: n = 1,088; 2009: n = 796; 2012: n = 436). Estimates were adjusted for a child’s age, sex, race/ethnicity, pubertal stage at the last follow-up visit, and baseline household wealth. TT, rs9939609 TT genotype; TA/AA, rs9939609 TA/AA genotypes.