Association of fetal FTO gene variants with maternal postload glucose levels in pregnancy.

Objective: The FTO rs9939609 variant is a major common genetic risk factor of adult obesity. We hypothesized that the rs9939609 variant of the fetus alters the plasma glucose (PG) levels during oral glucose tolerance test (OGTT) routinely performed between the 24-28th gestational week.

Methods: We analysed the data of mother-neonate pairs from our prior gestational diabetes mellitus (GDM) case-control study (Hungarian-Austrian set, n = 858) and the HAPO study European ancestry subset (HAPO-EUR, n = 1374) using pre-pregnancy body mass index (BMI) and maternal age as covariates. The rs8050136 (complete LD with rs9939609) was used in the HAPO-EUR data set.

Results: Fetal FTO variants were associated (dominant genetic model) with decreased maternal 60'min PG values (ß_{Hungarian-Austrian} = -1.39 mmol/L, p = 1.97*10^-4; ß_HAPO-EUR = -0.18 mmol/L, p = 4.36*10^-2; ß_combined = -0.33 mmol/L, p = 2.11*10^-4) and with reduced incremental area under glucose curve at OGTT (ß_{Hungarian-Austrian} =-1.70 mmol*h/L, p = 3.83*10^-4; ß_HAPO-EUR = -0.23 mmol*h/L, p = 2.91*10^-2; ß_combined = -0.39 mmol*h/L, p = 1.61*10^-4).

Conclusion: FTO risk variants carried by the fetus may indirectly influence maternal metabolism and could be associated with a flatter OGTT curve driven by the reduced 1 h postload PG levels in pregnancy.