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Hypospadias is one of the most common congenital external genital malformations, which is characterized by abnormal urethral meatus. However, the etiology remains to be incompletely understood.  HAAO  is a gene that encodes a protein, which catalyzes the synthesis of quinolinic acid, and has been identified as a risk gene for hypospadias. Thus, this study was conducted to elaborate the association between  HAAO  gene polymorphism rs3816183 T&amp;gt;C and hypospadias in the largest hypospadias cohort from Asia, including 577 patients and 654 healthy controls in China. The strength of interrelation was evaluated using 95% confidence intervals (CIs) and odds ratios (ORs). Based on the stratified analysis of hypospadias subtypes, it was found that the  HAAO  risk allele rs386183[T] enhances the susceptibility for hypospadias among patients with anterior/middle hypospadias subtypes (adjusted OR = 1.31, 95% CI = 1.05–1.64,  p  = 0.017). Enhanced risk of hypospadias in the entirety could not be demonstrated (OR = 1.20, 95% CI = 1.00–1.47,  p  = 0.054). In summary, our study found that the rs3816183[T] polymorphism is associated with increased risk of anterior/middle hypospadias among Southern Han Chinese children. The mechanisms by which the variations in the  HAAO  gene require further research.

HAAO rs3816183 Polymorphisms [T] Increase Anterior/Middle Hypospadias Risk in Southern Han Chinese Population