title: Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men.
abstract: Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men. A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22-24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas-positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate-specific antigen and neutral α-glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas-positive sperm, while men with longer GGN had higher oestradiol levels. These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear.
authors.affiliation: Department of Reproductive Molecular Medicine, Lund University, SE-20502 Malmö, Sweden. leon.brokken@med.lu.se
authors.forename: L J S
authors.initials: LJ
authors.lastname: Brokken
authors.forename: L
authors.initials: L
authors.lastname: Rylander
authors.forename: B A
authors.initials: BA
authors.lastname: Jönsson
authors.forename: M
authors.initials: M
authors.lastname: Spanò
authors.forename: H S
authors.initials: HS
authors.lastname: Pedersen
authors.forename: J K
authors.initials: JK
authors.lastname: Ludwicki
authors.forename: V
authors.initials: V
authors.lastname: Zviezdai
authors.forename: D
authors.initials: D
authors.lastname: Bizzaro
authors.forename: G C
authors.initials: GC
authors.lastname: Manicardi
authors.forename: G
authors.initials: G
authors.lastname: Toft
authors.forename: J P
authors.initials: JP
authors.lastname: Bonde
authors.forename: A
authors.initials: A
authors.lastname: Giwercman
authors.forename: Y
authors.initials: Y
authors.lastname: Lundberg Giwercman
mesh_terms: D015415:Biomarkers; D003430:Cross-Sectional Studies; D053938:DNA Fragmentation; D004958:Estradiol / Q000097:blood; D005298:Fertility / Q000235:genetics*; D056726:Genetic Association Studies; D005837:Genitalia, Male; D005838:Genotype; D006801:Humans; D007265:Inhibins / Q000032:analysis / Q000235:genetics; D004930:Inuit / Q000235:genetics*; D008297:Male; D010641:Phenotype; D017430:Prostate-Specific Antigen / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics*; D012098:Reproduction; D055101:Semen Analysis; D013076:Sperm Count; D018911:Trinucleotide Repeats / Q000235:genetics*; D044465:White People / Q000235:genetics*; D000520:alpha-Glucosidases / Q000378:metabolism; D019014:fas Receptor / Q000032:analysis
chemical_list: D015415:Biomarkers; D011944:Receptors, Androgen; D019014:fas Receptor; C422364:inhibin B; D004958:Estradiol; D007265:Inhibins; D000520:alpha-Glucosidases; D017430:Prostate-Specific Antigen