title: Hypospadias and variants in genes related to sex hormone biosynthesis and metabolism.
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.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Carmichael
authors.forename: J S
authors.initials: JS
authors.lastname: Witte
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: E J
authors.initials: EJ
authors.lastname: Lammer
authors.forename: G M
authors.initials: GM
authors.lastname: Shaw
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007021:Hypospadias / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000235:genetics; D010413:Penis / Q000002:abnormalities / Q000033:anatomy & histology; D020641:Polymorphism, Single Nucleotide; D011375:Progesterone Reductase / Q000096:biosynthesis / Q000235:genetics; D012306:Risk; D013251:Steroid Isomerases / Q000096:biosynthesis / Q000235:genetics; D043266:Steryl-Sulfatase / Q000096:biosynthesis / Q000235:genetics
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D002352:Carrier Proteins; D012739:Gonadal Steroid Hormones; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C105684:STARD3 protein, human; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3; D011375:Progesterone Reductase; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human; C584039:STS protein, human; D043266:Steryl-Sulfatase; D013251:Steroid Isomerases
keywords: gene polymorphism; hypospadias; sex hormones