In the current study, by testing the nearby SNP and conducting interaction analysis and mediation analysis, we identified that the HIF3A rs3826795 polymorphism interacts with obesity on ALT, and HIF3A DNA methylation could act as a mediator in the effect of rs3826795 on ALT in obese children. The gene discussed is HIF3A; the disease is obesity due to melanocortin 4 receptor deficiency.