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.
© 2013 American Society of Andrology and European Academy of Andrology.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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17-Hydroxysteroid Dehydrogenases / genetics*
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase / biosynthesis
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics
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Cytochrome P-450 CYP3A / biosynthesis
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Cytochrome P-450 CYP3A / genetics
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Genetic Predisposition to Disease
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Genetic Variation
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Genotype
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Gonadal Steroid Hormones / biosynthesis
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Gonadal Steroid Hormones / genetics*
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Gonadal Steroid Hormones / metabolism
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Humans
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Hypospadias / epidemiology
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Hypospadias / genetics*
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Male
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Multienzyme Complexes / biosynthesis
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Multienzyme Complexes / genetics
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Penis / abnormalities
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Penis / anatomy & histology
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Polymorphism, Single Nucleotide
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Progesterone Reductase / biosynthesis
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Progesterone Reductase / genetics
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Risk
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Steroid Isomerases / biosynthesis
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Steroid Isomerases / genetics
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Steryl-Sulfatase / biosynthesis
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Steryl-Sulfatase / genetics
Substances
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3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
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Carrier Proteins
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Gonadal Steroid Hormones
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Membrane Proteins
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Multienzyme Complexes
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STARD3 protein, human
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17-Hydroxysteroid Dehydrogenases
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17beta-hydroxysteroid dehydrogenase type 3
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Progesterone Reductase
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase
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SRD5A2 protein, human
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STS protein, human
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Steryl-Sulfatase
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Steroid Isomerases