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Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics

Giwercman, Aleksander LU ; Rylander, Lars LU ; Rignell-Hydbom, Anna LU ; Jönsson, Bo A LU ; Pedersen, Henning S.; Ludwicki, Jan K.; Lesovoy, Vladimir; Zvyezday, Valentyna; Spano, Marcello and Manicardi, Gian-Carlo, et al. (2007) In Pharmacogenetics & Genomics 17(6). p.391-401
Abstract
Objectives Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed to investigate whether the CAG and GGN polymorphisms in the androgen receptor gene modify the effect of persistent organohalogen pollutant exposure on human sperm characteristics. Methods Semen and blood from 680 men [mean (SD) age 34 (10) years] from Greenland, Sweden, Warsaw (Poland) and Kharkiv (Ukraine) were collected. Persistent organohalogen pollutant exposure was assessed by measuring serum levels of 2,2,4,4,5,5'-hexachlorobiphenyl (CB-153) and... (More)
Objectives Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed to investigate whether the CAG and GGN polymorphisms in the androgen receptor gene modify the effect of persistent organohalogen pollutant exposure on human sperm characteristics. Methods Semen and blood from 680 men [mean (SD) age 34 (10) years] from Greenland, Sweden, Warsaw (Poland) and Kharkiv (Ukraine) were collected. Persistent organohalogen pollutant exposure was assessed by measuring serum levels of 2,2,4,4,5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE). Semen characteristics (volume, sperm concentration, total count proportion of progressively motile and morphology) and DNA fragmentation index (DFI) were determined. CAG and GGN repeat lengths were determined by direct sequencing of leukocyte DNA. Results A statistically significant interaction was found between the CB-153 group and CAG repeat category in relation to sperm concentration and total sperm count (P=0.03 and 0.01, respectively). For p,p'-DDE, in the European cohorts a significant interaction was found in relation to DFI (P=0.01). For CAG<20, sperm concentration and total sperm count were 35 and 42% lower, respectively, when the group with CB-153 exposure above median was compared with that below the median. DF1 was 40% higher in the high p,p'-DDE exposure group for CAG < 21. Conclusions This study indicated that the androgen receptor CAG repeat length might modify the susceptibility of an individual to the adverse effects of persistent organohalogen pollutant exposure on semen quality. Other studies regarding this matter are warranted. (Less)
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published
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keywords
persistent organohalogen pollutants, gene-environment interaction, androgen receptor, CAG repeats, semen quality
in
Pharmacogenetics & Genomics
volume
17
issue
6
pages
391 - 401
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000246931900002
  • scopus:33847668918
ISSN
1744-6872
DOI
10.1097/01.fpc.0000236329.26551.78
language
English
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yes
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fabd45bf-4ed4-4654-baea-1a7d46b35813 (old id 650651)
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http://www.jpharmacogenetics.com/pt/re/pharmgen/abstract.01213011-200706000-00002.htm
date added to LUP
2007-12-11 21:24:13
date last changed
2017-08-27 03:47:39
@article{fabd45bf-4ed4-4654-baea-1a7d46b35813,
  abstract     = {Objectives Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed to investigate whether the CAG and GGN polymorphisms in the androgen receptor gene modify the effect of persistent organohalogen pollutant exposure on human sperm characteristics. Methods Semen and blood from 680 men [mean (SD) age 34 (10) years] from Greenland, Sweden, Warsaw (Poland) and Kharkiv (Ukraine) were collected. Persistent organohalogen pollutant exposure was assessed by measuring serum levels of 2,2,4,4,5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE). Semen characteristics (volume, sperm concentration, total count proportion of progressively motile and morphology) and DNA fragmentation index (DFI) were determined. CAG and GGN repeat lengths were determined by direct sequencing of leukocyte DNA. Results A statistically significant interaction was found between the CB-153 group and CAG repeat category in relation to sperm concentration and total sperm count (P=0.03 and 0.01, respectively). For p,p'-DDE, in the European cohorts a significant interaction was found in relation to DFI (P=0.01). For CAG&lt;20, sperm concentration and total sperm count were 35 and 42% lower, respectively, when the group with CB-153 exposure above median was compared with that below the median. DF1 was 40% higher in the high p,p'-DDE exposure group for CAG &lt; 21. Conclusions This study indicated that the androgen receptor CAG repeat length might modify the susceptibility of an individual to the adverse effects of persistent organohalogen pollutant exposure on semen quality. Other studies regarding this matter are warranted.},
  author       = {Giwercman, Aleksander and Rylander, Lars and Rignell-Hydbom, Anna and Jönsson, Bo A and Pedersen, Henning S. and Ludwicki, Jan K. and Lesovoy, Vladimir and Zvyezday, Valentyna and Spano, Marcello and Manicardi, Gian-Carlo and Bizzaro, Davide and Bonefeld-Jorgensen, Eva C. and Toft, Gunnar and Bonde, Jens Peter and Giwercman, Charlotte and Tiido, Tarmo and Giwercman, Yvonne},
  issn         = {1744-6872},
  keyword      = {persistent organohalogen pollutants,gene-environment interaction,androgen receptor,CAG repeats,semen quality},
  language     = {eng},
  number       = {6},
  pages        = {391--401},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Pharmacogenetics & Genomics},
  title        = {Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics},
  url          = {http://dx.doi.org/10.1097/01.fpc.0000236329.26551.78},
  volume       = {17},
  year         = {2007},
}