Association of ADIPOQ-rs2241766 and FTO-rs9939609 genetic variants with body mass index trajectory in women of reproductive age over 6 years of follow-up: the PREDI study

Background: Interindividual variations in body mass index (BMI) can be partially explained by genetic differences. We aimed to examine the association of the ADIPOQ-rs2241766, LEP-rs7799039 and FTO-rs9939609 genetic variants with BMI trajectory in women of reproductive age over 6 years of follow-up. Methods: This was a prospective study that used data from 435 women of the PREDI Study conducted in Brazil. Socioeconomic, biological and anthropometric data were collected at four time points: 2012 (baseline) in the maternity hospital, and 2013–14, 2016–17 and 2018 (1^st, 2^ndand 3^rdfollow-ups) at the participant’s home. Genotyping was performed by PCR-RFLP. Linear mixed-effect and Poisson regression models were used to address the association of ADIPOQ, LEPand FTOgenotypes with BMI and overweight/obesity status. Results: Women carrying the risk allele (TA or AA) of the FTO-rs9939609 genetic variant had a 1.16 kg/m²higher BMI over the follow-up period than those carrying the wild-type genotype (TT), even when adjusted for potential confounders (95% CI: 0.23–2.10, p= 0.015). The risk of obesity associated with the FTO-TA or AA genotype decreased over the years, demonstrating an influence of time on its trajectory (IRR = 0.99, 95% CI: 0.98–0.99, p= 0.016). There was no variation in BMI trajectories for the ADIPOQ-rs2241766, LEP-rs7799039 or FTO-rs9939609 genetic variant. Conclusions: The results of this study suggest that monitoring women of reproductive age with ADIPOQ-rs2241766 TG/GG or FTO-rs9939609 TA/AA genotypes may be an important strategy to reduce maternal excess body weight and, consequently, the long-term public health burden of obesity.