Polymorphisms in the P450 c17 (17-hydroxylase/17, 20-Lyase) gene: association with estradiol and testosterone concentration in hypospadias.

Objective: To investigate the association of CYP17 polymorphism with 17β-estradiol (E2) and testosterone (T) concentration in hypospadias.

Methods: Two-hundred twenty-three boys (91 with hypospadias and 132 age-matched controls) were included in the study. CYP17 polymorphism was evaluated using the polymerase chain reaction-restriction fragment length polymorphism method, whereas T and E2 levels were estimated in serum by enzyme-linked immunosorbent assay. Association between CYP17 genotypes and 17β-E2, T, and their ratio (E2/T) was analyzed by analysis of variance followed by Tukey's test. 17β-E2, T, and E2/T ratio was also compared among the different degrees of hypospadias, as well as in controls, by unpaired Student's t-test.

Results: Significantly low levels of T were observed in severe-degree hypospadias (n = 14; mean ± SD = 1.01 ± 0.57) compared with mild cases (n = 77; mean ± SD = 1.93 ± 1.40) and controls (mean ± SD = 3.32 ± 2.06) (P <.05). E2/T ratio was also significantly higher in hypospadias cases (5.36 ± 3.55) compared with controls (2.21 ± 2.52). Heterozygous variants (A1/A2) of CYP17 were present in higher frequency (OR = 0.96; 95% CI = .518-1.770) and homozygous (A2) variants were less frequently found in hypospadias (OR = 0.87; 95% CI = .363-2.077), but results were insignificant. No association between 17β-E2 and T with different CYP17 genotypes was observed.

Conclusion: Our study suggests that, although polymorphism in CYP17 gene may not be associated with 17β-E2 and T concentrations in hypospadias cases, low levels of T and higher E2/T ratio might possibly act as risk factors for hypospadias.