Increased hypospadias risk by rs3743104[G] in the southern Han Chinese population.

Hypospadias is a common congenital genitourinary malformation characterized by ventral opening of the urethral meatus. As a member of the bone morphogenic protein antagonist family, has been identified as associated with susceptibility to hypospadias in the European population. The present study was designed to elaborate on the mutual relationship between replicated single-nucleotide polymorphisms (SNPs) and hypospadias in Asia's largest case-control study in the Southern Han Chinese population involving 577 patients and 654 controls. Our results demonstrate that the risk allele rs3743104[G] markedly increases the risk of mild/moderate and severe hypospadias (, 0.280.66). GTEx expression quantitative trait locus data revealed that the eQTL SNP rs3743104 has more associations of eQTL SNP rs3743104 and targets in pituitary tissues. Additionally, Bioinformatics and Luciferase Assays show that miR-182 is identified as a suppressor for expression, likely through regulation of its binding affinity to rs3743104 locus. In conclusion, the risk allele rs3743104[G] increases hypospadias susceptibility in mild/moderate and severe cases among the southern Han population. rs3743104 regulates expression by altering the binding affinity of miR-182 to their locus. Collectively, this study provides new evidence that rs3743104 is associated with an increased risk of hypospadias. These findings provide a promising biomarker and merit further exploration.