We used the AFP and free beta-HCG levels separately to predict fetuses with hypospadias, and the AUCs were 0.644 (95% Confidence interval (CI): 0.5500.737, P = .005) and 0.659 (95% CI: 0.5650.752, P = .002), respectively.
In the ITA study group, two SNPs in AHR (rs3757824) and ARNT2 (rs1020397) were significantly associated with risk of CO. Interaction analysis of the positive SNPs using multifactor dimensionality reduction demonstrated that synergistic interaction between rs2472680, rs4919686 and rs5000770 had 62.81% prediction accuracy for CO (P=0.011) and that between rs2069521 and rs2278705 had 69.98% prediction accuracy for HS (P=0.001) in JPN population.
Mutations in the genes of penile development (e.g., HOX, FGF, Shh) and testicular determination (e.g., WT1, SRY), luteinizing hormone receptor, and androgen receptor have also been proposed to be implicated in hypospadias.
The genes of penile development (HOX, FGF, Shh) and testicular determination (WT1, SRY) and those regulating the synthesis [luteinizing hormone (LH) receptor] and action of androgen (5alpha reductase, androgen receptor) can cause hypospadias if altered.
Endogenous endocrine abnormalities identified so far include testosterone biosynthesis defects, 5alpha-reductase type 2 mutations, and androgen receptor mutations (the rarest cause, even in cases of severe hypospadias).
These rats in one group received the androgen receptor antagonist flutamide (25 mg/kg/day) from gestation days 11-17, to establish a rat model of hypospadias for further study of the molecular mechanisms of the hypospadias etiology.
To test this hypothesis we measured estrogen and androgen formation in two brothers with perineoscrotal hypospadias and severe gynecomastia (the Reifenstein phenotype) due to a mutation that impairs androgen receptor function.
To investigate the prevalence of genetic mutations in steroid 5α-reductase-2 (SRD5A2), androgen receptor (AR) and steroidogenic factor-1 (SF-1) in Chinese children with hypospadias, and to also explore the possible underlying molecular mechanisms of this disease.
To examine the possibility that androgen receptor defects are a common cause of such deficiencies, we have determined the coding sequence of the androgen receptor gene in nine patients with severe hypospadias.
Remarkably low incidence of hypospadias in Greenland despite high exposure to endocrine disrupters; possible protective effect of androgen receptor genotype.
Co-regulators of the androgen receptor start being acknowledged as possible candidates for hormone-resistance instances, which could account for hypospadias.
Isolated distal shaft hypospadias is associated with mutations of the androgen receptor gene but these mutations appear to be a rare cause of hypospadias.
This finding indicates that AR genotype could contribute to a genetic predisposition in Greenlanders, who despite one of the worlds highest body burden of POPs, seem to be protected from hypospadias.
The correlation between the level of androgen receptor mRNA expression and the penile size was almost statistically significant only in hypospadias patients (r=0.47; p=0.053).
The results showed that patients with isolated hypospadias had longer CAG repeats in their androgen receptor gene sequence (weighted mean difference = 1.36, 95% confidence interval = 0.60-2.13; P = 0.0005).