CONTEXT: Hypospadias is a common congenital malformation of the male external genitalia with a multifactorial etiology. Little is known about the genes involved in hypospadias. A few genetic associations have been reported but mainly in studies of small sample size. Most of these associations have not been replicated. OBJECTIVE: The aim of this study was to investigate whether previously reported associations for four single-nucleotide polymorphisms (SNPs) in genes involved in hormonal pathways could be replicated in a large Dutch hypospadias sample. The SNPs investigated are rs523349 in steroid-5 alpha-reductase (SRD5A2), rs6932902 in estrogen receptor 1 (ESR1), rs2987983 in ESR2, and rs11119982 in activating transcription factor 3 (ATF3). DESIGN, PARTICIPANTS, AND METHODS: We genotyped 620 Caucasian hypospadias cases and 596 controls for these SNPs using TaqMan-based genotyping. RESULTS: We did not replicate the associations of the SNPs in SRD5A2 and ESR1 with hypospadias. The SNPs in ESR2 and ATF3 were borderline associated with hypospadias [odds ratios 0.9 (95% confidence interval 0.7-1.0) and 1.2 (95% confidence interval 1.0-1.4), respectively] but in the opposite direction compared with earlier publications. Stratification according to localization of the urethral opening produced comparable results in the subgroups. CONCLUSIONS: The lack of consistency between our and previously performed studies might represent spurious results or chance findings in our or the earlier studies, differences in criteria used to select the study populations, or a real difference between populations, i.e. different genes contributing to disease risk. These results once again confirm the importance of replication in genetic association approaches.
CONTEXT: Hypospadias is a common congenital malformation of the male external genitalia with a multifactorial etiology. Little is known about the genes involved in hypospadias. A few genetic associations have been reported but mainly in studies of small sample size. Most of these associations have not been replicated. OBJECTIVE: The aim of this study was to investigate whether previously reported associations for four single-nucleotide polymorphisms (SNPs) in genes involved in hormonal pathways could be replicated in a large Dutch hypospadias sample. The SNPs investigated are rs523349 in steroid-5 alpha-reductase (SRD5A2), rs6932902 in estrogen receptor 1 (ESR1), rs2987983 in ESR2, and rs11119982 in activating transcription factor 3 (ATF3). DESIGN, PARTICIPANTS, AND METHODS: We genotyped 620 Caucasian hypospadias cases and 596 controls for these SNPs using TaqMan-based genotyping. RESULTS: We did not replicate the associations of the SNPs in SRD5A2 and ESR1 with hypospadias. The SNPs in ESR2 and ATF3 were borderline associated with hypospadias [odds ratios 0.9 (95% confidence interval 0.7-1.0) and 1.2 (95% confidence interval 1.0-1.4), respectively] but in the opposite direction compared with earlier publications. Stratification according to localization of the urethral opening produced comparable results in the subgroups. CONCLUSIONS: The lack of consistency between our and previously performed studies might represent spurious results or chance findings in our or the earlier studies, differences in criteria used to select the study populations, or a real difference between populations, i.e. different genes contributing to disease risk. These results once again confirm the importance of replication in genetic association approaches.
Authors: Luke C Govers; Tiffany R Phillips; Deidre M Mattiske; Nineveh Rashoo; Jay R Black; Adriane Sinclair; Laurence S Baskin; Gail P Risbridger; Andrew J Pask Journal: FASEB J Date: 2019-06-21 Impact factor: 5.191
Authors: Loes F M van der Zanden; Iris A L M van Rooij; Wout F J Feitz; Jo Knight; A Rogier T Donders; Kirsten Y Renkema; Ernie M H F Bongers; Sita H H M Vermeulen; Lambertus A L M Kiemeney; Joris A Veltman; Alejandro Arias-Vásquez; Xufeng Zhang; Ellen Markljung; Liang Qiao; Laurence S Baskin; Agneta Nordenskjöld; Nel Roeleveld; Barbara Franke; Nine V A M Knoers Journal: Nat Genet Date: 2010-11-28 Impact factor: 38.330
Authors: Loes F M van der Zanden; Tessel E Galesloot; Wout F J Feitz; Marijn M Brouwers; Min Shi; Nine V A M Knoers; Barbara Franke; Nel Roeleveld; Iris A L M van Rooij Journal: J Urol Date: 2012-10-22 Impact factor: 7.450
Authors: Slimane Allali; Jean-Baptiste Muller; Raja Brauner; Diana Lourenço; Radia Boudjenah; Vasiliki Karageorgou; Christine Trivin; Henri Lottmann; Stephen Lortat-Jacob; Claire Nihoul-Fékété; Olivier De Dreuzy; Ken McElreavey; Anu Bashamboo Journal: PLoS One Date: 2011-10-20 Impact factor: 3.240