title: Androgen receptor polyglutamine repeat length (AR-CAGn) modulates the effect of testosterone on androgen-associated somatic traits in Filipino young adult men.
abstract: The androgen receptor (AR) mediates expression of androgen-associated somatic traits such as muscle mass and strength. Within the human AR is a highly variable glutamine short-tandem repeat (AR-CAGn), and CAG repeat number has been inversely correlated to AR transcriptional activity in vitro. However, evidence for an attenuating effect of long AR-CAGn on androgen-associated somatic traits has been inconsistent in human populations. One possible explanation for this lack of consistency is that the effect of AR-CAGn on AR bioactivity in target tissues likely varies in relation to circulating androgen levels.
  
  
  
  We tested whether relationships between AR-CAGn and several androgen-associated somatic traits (waist circumference, lean mass, arm muscle area, and grip strength) were modified by salivary (waking and pre-bed) and circulating (total) testosterone (T) levels in young adult males living in metropolitan Cebu, Philippines (n = 675).
  
  
  
  When men's waking T was low, they had a reduction in three out of four androgen-associated somatic traits with lengthening AR-CAGn (p < .1), consistent with in vitro research. However, when waking T was high, we observed the opposite effect-lengthening AR-CAGn was associated with an increase in these same somatic traits.
  
  
  
  Our finding that longer AR-CAGn predicts greater androgen-associated trait expression among high-T men runs counter to in vitro work, but is generally consistent with the few prior studies to evaluate similar interactions in human populations. Collectively, these results raise questions about the applicability of findings derived from in vitro AR-CAGn studies to the receptor's role in maintaining androgen-associated somatic traits in human populations.
authors.affiliation: Department of Anthropology, Northwestern University, Evanston, Illinois.
authors.forename: Calen P
authors.identifier: 0000-0002-0550-7949
authors.initials: CP
authors.lastname: Ryan
authors.affiliation: Department of Anthropology, Northwestern University, Evanston, Illinois.
authors.forename: Alexander V
authors.identifier: 0000-0001-5622-3826
authors.initials: AV
authors.lastname: Georgiev
authors.affiliation: Department of Anthropology, Northwestern University, Evanston, Illinois.|Institute for Policy Research, Northwestern University, Evanston, Illinois.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: McDade
authors.affiliation: Department of Anthropology, University of Notre Dame, Notre Dame, Indiana.|The Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana.
authors.forename: Lee T
authors.initials: LT
authors.lastname: Gettler
authors.affiliation: Department of Anthropology, University of Washington, Seattle, Washington.|Center for Studies in Demography and Ecology, University of Washington, Seattle, Washington.
authors.forename: Dan T A
authors.initials: DTA
authors.lastname: Eisenberg
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Margarita
authors.initials: M
authors.lastname: Rzhetskaya
authors.affiliation: USC-Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines.
authors.forename: Sonny S
authors.initials: SS
authors.lastname: Agustin
authors.affiliation: Department of Anthropology, Northwestern University, Evanston, Illinois.|Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.|Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
authors.affiliation: Department of Anthropology, Northwestern University, Evanston, Illinois.|Institute for Policy Research, Northwestern University, Evanston, Illinois.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Kuzawa
mesh_terms: D000328:Adult; D000728:Androgens / Q000378:metabolism*; D001823:Body Composition / Q000235:genetics; D018737:Hand Strength; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D018482:Muscle, Skeletal / Q000378:metabolism*; D010455:Peptides; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics*; D012463:Saliva / Q000737:chemistry; D012727:Sex Characteristics; D013739:Testosterone / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D055105:Waist Circumference / Q000235:genetics*; D055815:Young Adult
chemical_list: C410798:AR protein, human; D000728:Androgens; D010455:Peptides; D011944:Receptors, Androgen; C097188:polyglutamine; D013739:Testosterone
keywords: androgens; body composition; sexual dimorphism; short-tandem repeats