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Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene

Aschim, EL; Nordenskjold, A; Giwercman, Aleksander LU ; Lundin, Kristina LU ; Ruhayel, Yasir LU ; Haugen, TB; Grotmol, T and Giwercman, Yvonne LU (2004) In Journal of Clinical Endocrinology and Metabolism 89(10). p.5105-5109
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
89
issue
10
pages
5105 - 5109
publisher
The Endocrine Society
external identifiers
  • wos:000224326300050
  • pmid:15472213
  • scopus:6344229471
ISSN
1945-7197
DOI
10.1210/jc.2004-0293
language
English
LU publication?
yes
id
41e42036-07be-4089-bb60-f453d6243114 (old id 898347)
date added to LUP
2008-01-10 11:05:54
date last changed
2017-10-01 04:34:34
@article{41e42036-07be-4089-bb60-f453d6243114,
  abstract     = {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.},
  author       = {Aschim, EL and Nordenskjold, A and Giwercman, Aleksander and Lundin, Kristina and Ruhayel, Yasir and Haugen, TB and Grotmol, T and Giwercman, Yvonne},
  issn         = {1945-7197},
  language     = {eng},
  number       = {10},
  pages        = {5105--5109},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene},
  url          = {http://dx.doi.org/10.1210/jc.2004-0293},
  volume       = {89},
  year         = {2004},
}