title: Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics.
abstract: OBJECTIVE
  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. DFI was 40% higher in the high p,p'-DDE exposure group for CAG<or=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.
authors.affiliation: Molecular Reproductive Medicine Research Unit, Department of Clinical Sciences, Reproductive Medicine Centre, Malmö University Hospital, Lund University, Malmö, Sweden. aleksander.giwercman@med.lu.se
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.forename: Lars
authors.initials: L
authors.lastname: Rylander
authors.forename: Anna
authors.initials: A
authors.lastname: Rignell-Hydbom
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.forename: Henning S
authors.initials: HS
authors.lastname: Pedersen
authors.forename: Jan K
authors.initials: JK
authors.lastname: Ludwicki
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lesovoy
authors.forename: Valentyna
authors.initials: V
authors.lastname: Zvyezday
authors.forename: Marcello
authors.initials: M
authors.lastname: Spano
authors.forename: Gian-Carlo
authors.initials: GC
authors.lastname: Manicardi
authors.forename: Davide
authors.initials: D
authors.lastname: Bizzaro
authors.forename: Eva C
authors.initials: EC
authors.lastname: Bonefeld-Jørgensen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Toft
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Bonde
authors.forename: Charlotte
authors.initials: C
authors.lastname: Giwercman
authors.forename: Tarmo
authors.initials: T
authors.lastname: Tiido
authors.forename: Yvonne Lundberg
authors.initials: YL
authors.lastname: Giwercman
mesh_terms: D000328:Adult; D053938:DNA Fragmentation / Q000187:drug effects; D003633:Dichlorodiphenyl Dichloroethylene / Q000097:blood / Q000633:toxicity; D052244:Endocrine Disruptors / Q000097:blood / Q000633:toxicity; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008297:Male; D018598:Minisatellite Repeats; D010597:Pharmacogenetics; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D012661:Semen / Q000187:drug effects* / Q000378:metabolism*; D013076:Sperm Count; D018911:Trinucleotide Repeats
chemical_list: C410798:AR protein, human; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D006846:Hydrocarbons, Halogenated; D011944:Receptors, Androgen; D003633:Dichlorodiphenyl Dichloroethylene; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl