The SNPs in ESR2 and ATF3 were borderline associated with hypospadias [odds ratios 0.9 (95% confidence interval 0.7-1.0) and 1.2 (95% confidence interval 1.0-1.4), respectively] but in the opposite direction compared with earlier publications.
Mastermind-like domain containing 1/chromosome X open reading frame 6 mutation and activating transcription factor 3 variants have been shown to be associated with the incidence of isolated hypospadias.
ATF3 is involved in the TGF-beta epithelial-mesenchymal signaling pathway, and its involvement in hypospadias suggests that ATF3 plays a role in development of this anomaly as a result of exposure to estrogenic compounds.
Our results indicate that ATF3 is up-regulated in the penile skin tissues of boys with hypospadias, suggesting a role for this transcription factor in the development of this abnormality.