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Non-linear association between androgen receptor CAG repeat length and risk of male subfertility - a meta-analysis.

Nenonen, Hannah LU ; Giwercman, Aleksander LU ; Hallengren, E and Giwercman, Yvonne LU (2011) In International journal of andrology Jul 1. p.327-332
Abstract
Summary The CAG repeat in the androgen receptor (AR) has been widely studied in association with male infertility, but the results are conflicting. In a recent meta-analysis, infertile men had <1 repeat longer CAG stretch than fertile men when analysed in a linear regression model assuming that AR function diminishes with increasing CAG length. However, in vitro, a non-linear activity pattern was recently demonstrated so that ARs containing short and long stretches, respectively, displayed lower activity than the AR of median length. These results prompted us to explore the possible association between CAG number and male infertility risk in a stratified manner on the basis of data from the mentioned meta-analysis and subjects from our... (More)
Summary The CAG repeat in the androgen receptor (AR) has been widely studied in association with male infertility, but the results are conflicting. In a recent meta-analysis, infertile men had <1 repeat longer CAG stretch than fertile men when analysed in a linear regression model assuming that AR function diminishes with increasing CAG length. However, in vitro, a non-linear activity pattern was recently demonstrated so that ARs containing short and long stretches, respectively, displayed lower activity than the AR of median length. These results prompted us to explore the possible association between CAG number and male infertility risk in a stratified manner on the basis of data from the mentioned meta-analysis and subjects from our clinical unit. The study population included 3915 men, 1831 fertile and 2084 infertile. Data were divided into three categories: CAG < 22, CAG 22-23 (reference) and CAG > 23 and analysed in a binary logistic regression model. Men with CAG < 22 and CAG > 23 had 20% increased odds ratio of infertility compared with carriers of the median lengths [for CAG < 22: p = 0.03, 95% confidence interval (CI): 1.02-1.39; for CAG > 23: p = 0.02, 95% CI: 1.03-1.44]. These results show that an alternative model to a linear one for the genotype-phenotype association in relation to AR CAG repeats is likely, as lengths close to the median confine lowest risk of infertility. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International journal of andrology
volume
Jul 1
pages
327 - 332
publisher
Wiley-Blackwell
external identifiers
  • wos:000292889200005
  • pmid:20579136
  • scopus:79960171305
ISSN
1365-2605
DOI
10.1111/j.1365-2605.2010.01084.x
language
English
LU publication?
yes
id
fdd47ecd-77b0-4f53-84a0-cfa7c8b3d3d4 (old id 1625689)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20579136?dopt=Abstract
date added to LUP
2010-07-01 22:41:35
date last changed
2017-04-30 16:10:29
@article{fdd47ecd-77b0-4f53-84a0-cfa7c8b3d3d4,
  abstract     = {Summary The CAG repeat in the androgen receptor (AR) has been widely studied in association with male infertility, but the results are conflicting. In a recent meta-analysis, infertile men had &lt;1 repeat longer CAG stretch than fertile men when analysed in a linear regression model assuming that AR function diminishes with increasing CAG length. However, in vitro, a non-linear activity pattern was recently demonstrated so that ARs containing short and long stretches, respectively, displayed lower activity than the AR of median length. These results prompted us to explore the possible association between CAG number and male infertility risk in a stratified manner on the basis of data from the mentioned meta-analysis and subjects from our clinical unit. The study population included 3915 men, 1831 fertile and 2084 infertile. Data were divided into three categories: CAG &lt; 22, CAG 22-23 (reference) and CAG &gt; 23 and analysed in a binary logistic regression model. Men with CAG &lt; 22 and CAG &gt; 23 had 20% increased odds ratio of infertility compared with carriers of the median lengths [for CAG &lt; 22: p = 0.03, 95% confidence interval (CI): 1.02-1.39; for CAG &gt; 23: p = 0.02, 95% CI: 1.03-1.44]. These results show that an alternative model to a linear one for the genotype-phenotype association in relation to AR CAG repeats is likely, as lengths close to the median confine lowest risk of infertility.},
  author       = {Nenonen, Hannah and Giwercman, Aleksander and Hallengren, E and Giwercman, Yvonne},
  issn         = {1365-2605},
  language     = {eng},
  pages        = {327--332},
  publisher    = {Wiley-Blackwell},
  series       = {International journal of andrology},
  title        = {Non-linear association between androgen receptor CAG repeat length and risk of male subfertility - a meta-analysis.},
  url          = {http://dx.doi.org/10.1111/j.1365-2605.2010.01084.x},
  volume       = {Jul 1},
  year         = {2011},
}