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ABSTRACT Aims: The aim of this study was investigation of the mediator role of the IRX3 gene in the relationship between the FTO gene and obesity. Materials and Methods: All related articles published in English from June 1990 to February 2017 were studied. Results: Only a Few studies have examined the association between the IRX3 gene with the FTO gene and obesity. However, all of them reported that the FTO gene can influence on the IRX3 gene expression. Also, it’s reported that the IRX3 gene expression level have a significant association with body weight and body composition. Conclusions: The FTO gene effects on obesity is in part due to its impact on the IRX3 gene expression level. The further studies are needed to investigate this interaction and clarify the existing mechanisms.