This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aschim, E. L. Articles by Giwercman, Y. L. Search for Related Content PubMed PubMed Citation Articles by Aschim, E. L. Articles by Giwercman, Y. L.

Linkage between Cryptorchidism, Hypospadias, and GGN Repeat Length in the Androgen Receptor Gene

Department of Gynaecology and Obstetrics (E.L.A., T.B.H.), Andrology Laboratory, Rikshospitalet University Hospital, N 0027 Oslo, Norway; Department of Molecular Medicine (A.N.), Karolinska Hospital, SE 171 76 Stockholm, Sweden; Fertility Centre (A.G., K.B.L., Y.R.) and Department of Urology (K.B.L., Y.L.G.), Malmö University Hospital, Lund University, SE 205 02 Malmö, Sweden; and Cancer Registry of Norway (T.G.), N 0310 Oslo, Norway

Address all correspondence and requests for reprints to: Elin L. Aschim, Andrology Laboratory, Department of Gynaecology and Obstetrics, Rikshospitalet University Hospital, N-0027 Oslo, Norway. E-mail: elaschim{at}biokjemi.uio.no; or Yvonne Giwercman, Malmö University Hospital, Entrance 46, floor 4, SE 205 02 Malmö, Sweden

Although sufficient androgen receptor (AR) function is crucial for normal male sexual differentiation, single-point mutations in the AR gene are infrequent in the two most common male congenital malformations, hypospadias and cryptorchidism. Because polymorphic CAG and GGN segments regulate AR function, we investigated whether there was any association between these polymorphisms and mentioned malformations. Genotyping was performed by direct sequencing of DNA from patients diagnosed with hypospadias (n = 51) and cryptorchidism (n = 23) and controls (n = 210). The subjects with hypospadias were divided into subgroups of glanular, penile, and penoscrotal hypospadias. Median GGN lengths were significantly higher (24 vs. 23) among both subjects with cryptorchidism, compared with controls (P = 0.001), and those with penile hypospadias, compared with either controls (P = 0.003) or glanular and penoscrotal hypospadias combined (P = 0.018). The frequency of cases with GGN 24 or more vs. GGN = 23, differed significantly among those with cryptorchidism (65/35%), compared with controls (31/54%) (P = 0.012), and among subjects with penile hypospadias (69/31%), compared with either controls (P = 0.035) or glanular or penoscrotal hypospadias combined (32/55%) (P = 0.056). There were no significant differences in CAG lengths between the cases and controls. Our findings indicate an association between GGN length and the risk of cryptorchidism and penile hypospadias, both conditions considered consequences of low androgenicity.

This article has been cited by other articles:

				V. Bogaert, G. Vanbillemont, Y. Taes, D. De Bacquer, E. Deschepper, K. Van Steen, and J.-M. Kaufman Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men Eur. J. Endocrinol., July 1, 2009; 161(1): 171 - 177. [Abstract] [Full Text] [PDF]

				I. A Hughes and C. L Acerini Factors controlling testis descent Eur. J. Endocrinol., December 1, 2008; 159(suppl_1): S75 - S82. [Abstract] [Full Text] [PDF]

				C. Foresta, D. Zuccarello, A. Garolla, and A. Ferlin Role of Hormones, Genes, and Environment in Human Cryptorchidism Endocr. Rev., August 1, 2008; 29(5): 560 - 580. [Abstract] [Full Text] [PDF]

				S. Ban, F. Sata, N. Kurahashi, S. Kasai, K. Moriya, H. Kakizaki, K. Nonomura, and R. Kishi Genetic polymorphisms of ESR1 and ESR2 that may influence estrogen activity and the risk of hypospadias Hum. Reprod., June 1, 2008; 23(6): 1466 - 1471. [Abstract] [Full Text] [PDF]

				H.E. Virtanen and J. Toppari Epidemiology and pathogenesis of cryptorchidism Hum. Reprod. Update, January 1, 2008; 14(1): 49 - 58. [Abstract] [Full Text] [PDF]

				F. F Brockschmidt, M. M Nothen, and A. M Hillmer The two most common alleles of the coding GGN repeat in the androgen receptor gene cause differences in protein function J. Mol. Endocrinol., July 1, 2007; 39(1): 1 - 8. [Abstract] [Full Text] [PDF]

				T. Tiido, A. Rignell-Hydbom, B.A.G. Jonsson, L. Rylander, A. Giwercman, and Y.L. Giwercman Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y : X ratio Mol. Hum. Reprod., April 1, 2007; 13(4): 223 - 229. [Abstract] [Full Text] [PDF]

				R. Radpour, M. Rezaee, A. Tavasoly, S. Solati, and A. Saleki Association of Long Polyglycine Tracts (GGN Repeats) in Exon 1 of the Androgen Receptor Gene With Cryptorchidism and Penile Hypospadias in Iranian Patients J Androl, January 1, 2007; 28(1): 164 - 169. [Abstract] [Full Text] [PDF]

				K B Lundin, Y L Giwercman, L Rylander, L Hagmar, and A Giwercman Androgen receptor gene GGN repeat length and reproductive characteristics in young Swedish men. Eur. J. Endocrinol., August 1, 2006; 155(2): 347 - 354. [Abstract] [Full Text] [PDF]

				K. B. Lundin, A. Nordenskjold, A. Giwercman, and Y. L. Giwercman Frequent Finding of the Androgen Receptor A645D Variant in Normal Population J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3228 - 3231. [Abstract] [Full Text] [PDF]

				E. Rajpert-De Meyts Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects Hum. Reprod. Update, May 1, 2006; 12(3): 303 - 323. [Abstract] [Full Text] [PDF]