Hypospadias and variants in genes related to sex hormone biosynthesis and metabolism

Andrology. 2014 Jan;2(1):130-7. doi: 10.1111/j.2047-2927.2013.00165.x. Epub 2013 Nov 26.

Abstract

We examined whether variants in genes related to sex hormone biosynthesis and metabolism were associated with hypospadias in humans. We examined 332 relatively common tag single-nucleotide polymorphisms (tagSNPs) in 20 genes. Analyses included 633 cases (84 mild, 322 moderate, 212 severe and 15 undetermined severity) and 855 population-based non-malformed male controls born in California from 1990 to 2003. We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for each SNP. Several of the 332 studied SNPs had p < 0.01: one in CYP3A4, four in HSD17B3, one in HSD3B1, two in STARD3, 10 in SRD5A2 and seven in STS. In addition, haplotype analyses gave several associations with p < 0.01. For HSD17B3, 14-SNP and 5-SNP blocks had ORs of 1.5 (95% CI 1.1, 2.0, p < 0.001) and 2.8 (95% CI 1.6, 4.8, p < 0.001) respectively. For SRD5A2, 9-SNP, 3-SNP and 8-SNP blocks had ORs of 1.7 (95% CI 1.3, 2.2, p < 0.001), 1.4 (95% CI 1.1, 1.8, p = 0.008) and 1.5 (95% CI 1.2, 1.9, p = 0.002) respectively. Our study indicates that several genes that contribute to sex hormone biosynthesis and metabolism are associated with hypospadias risk.

Keywords: gene polymorphism; hypospadias; sex hormones.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / genetics*
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / biosynthesis
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Cytochrome P-450 CYP3A / biosynthesis
  • Cytochrome P-450 CYP3A / genetics
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Gonadal Steroid Hormones / biosynthesis
  • Gonadal Steroid Hormones / genetics*
  • Gonadal Steroid Hormones / metabolism
  • Humans
  • Hypospadias / epidemiology
  • Hypospadias / genetics*
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Multienzyme Complexes / biosynthesis
  • Multienzyme Complexes / genetics
  • Penis / abnormalities
  • Penis / anatomy & histology
  • Polymorphism, Single Nucleotide
  • Progesterone Reductase / biosynthesis
  • Progesterone Reductase / genetics
  • Risk
  • Steroid Isomerases / biosynthesis
  • Steroid Isomerases / genetics
  • Steryl-Sulfatase / biosynthesis
  • Steryl-Sulfatase / genetics

Substances

  • 3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
  • Carrier Proteins
  • Gonadal Steroid Hormones
  • Membrane Proteins
  • Multienzyme Complexes
  • STARD3 protein, human
  • 17-Hydroxysteroid Dehydrogenases
  • 17beta-hydroxysteroid dehydrogenase type 3
  • Progesterone Reductase
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • SRD5A2 protein, human
  • STS protein, human
  • Steryl-Sulfatase
  • Steroid Isomerases