My lab has focused on the etilogy of hypospadias. In prospective clinical studies through our PCRC (now CTSI) we have shown that defects in androgen metabolism are a rare form of hypospadias and account for only a tiny minority of patents with hypospadias. We have identified a number of genes in humans that are associated with increased risk of hypospadias. We contimue to collect and bank blood, DNA and serum from all our patients with hypospasdias and colloborate with mutlple investigators on genetic projects. We were the first to report on an epigenetic DNA methylation abnormaltiies as a possible etiolog of hypospadias. Finally, we have extensively reviewed the human data on endocrine disruptors as the etilogy of hypospadsias the hypothesis of this proposal.
Baskin LS, Colborn T, Himes K. Hypospadias and endocrine disruption: is there a connection? Environmental health perspectives. 2001;109:1175-83.
Holmes NM, Miller WL, Baskin LS. Lack of defects in androgen production in children with hypospadias. The Journal of clinical endocrinology and metabolism. 2004 Jun;89(6):2811-6. PubMed PMID: 15181062.
Geller F, Feenstra B, Carstensen L, Pers TH, van Rooij IA, Korberg IB, et al. Genome-wide association analyses identify variants in developmental genes associated with hypospadias. Nature genetics. 2014 Sep;46(9):957-63. PubMed PMID: 25108383.
Kalfa N, Liu B, Klein O, Audran F, Wang MH, Mei C, et al. Mutations of CXorf6 are associated with a range of severities of hypospadias. Eur J Endocrinol. 2008 Oct;159(4):453-8. PubMed PMID: 18635673. Epub 2008/07/19. eng.
Kalfa N, Liu B, Klein O, Wang MH, Cao M, Baskin LS. Genomic variants of ATF3 in patients with hypospadias. The Journal of urology. 2008 Nov;180(5):2183-8; discussion 8. PubMed PMID: 18804813. Epub 2008/09/23. eng.
Liu B, Wang Z, Lin G, Agras K, Ebbers M, Willingham E, et al. Activating transcription factor 3 is up-regulated in patients with hypospadias. Pediatr Res. 2005 Dec;58(6):1280-3. PubMed PMID: 16306208.
Qiao L, Tasian GE, Zhang H, Cunha GR, Baskin L. ZEB1 is Estrogen Responsive in vitro in Human Foreskin Cells and is Overexpressed in Penile Skin in Patients with Severe Hypospadias. The Journal of urology. 2010.
Willingham E, Baskin LS. Candidate genes and their response to environmental agents in the etiology of hypospadias. Nat Clin Pract Urol. 2007 May;4(5):270-9. PubMed PMID: 17483812.
Choudhry S, Baskin LS, Lammer EJ, Witte JS, Dasgupta S, Ma C, et al. Genetic Polymorphisms in ESR1 and ESR2 Genes and Risk of Hypospadias in a Multi-ethnic Study Population. The Journal of urology. 2014 Nov 21. PubMed PMID: 25463985.
Choudhry S, Deshpande A, Qiao L, Beckman K, Sen S, Baskin LS. Genome-wide DNA methylation profiling of CpG islands in hypospadias. The Journal of urology. 2012 Oct;188(4 Suppl):1450-5. PubMed PMID: 22906644. Pubmed Central PMCID: 3725975.
Yiee JH, Baskin LS. Environmental factors in genitourinary development. The Journal of urology. 2010 Jul;184(1):34-41. PubMed PMID: 20478588.