title: The androgen receptor CAG repeat modifies the impact of testosterone on insulin resistance in women with polycystic ovary syndrome.
abstract: OBJECTIVE
  Hyperandrogenism is a central feature of the polycystic ovary syndrome (PCOS) and might worsen insulin resistance (IR) often seen in PCOS. Androgens act through the androgen receptor (AR). A polymorphic CAG repeat sequence within the AR gene was reported to modulate its transactivation activity. Therefore, we investigated a putative interaction between testosterone and the CAG repeat length polymorphism with respect to IR.
  
  
  METHODS
  In 63 PCOS women with normal glucose tolerance free testosterone, the biallelic CAG repeat length and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR as indicated by the homeostasis model assessment of IR (HOMA-IR).
  
  
  RESULTS
  Free testosterone was correlated with HOMA-IR. The impact of testosterone on HOMA-IR was modified by the AR CAG length as indicated by an interaction term. This interaction remained significant after adjustment for smoking, age and body mass index. While there was a positive association of free testosterone with HOMA-IR, the interaction term was inversely associated. The model, which explained 42.5% of the variation of HOMA-IR predicted that in carriers of short CAG lengths, an increase in testosterone increased IR. This effect attenuated with rising biallelic CAG length until it turns into the opposite at a CAG length longer than 23. The results were confirmed by using CIGMA as another measure of IR.
  
  
  CONCLUSIONS
  The association between testosterone and IR is modified by the CAG repeat polymorphism within the AR. Therefore, the evaluation of testosterone effects on IR seems to require consideration of the AR CAG repeat polymorphism in PCOS women.
authors.affiliation: Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Möhlig
authors.forename: Annette
authors.initials: A
authors.lastname: Jürgens
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Kurt
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Martin O
authors.initials: MO
authors.lastname: Weickert
authors.forename: Hans W
authors.initials: HW
authors.lastname: Schlösser
authors.forename: Thilo
authors.initials: T
authors.lastname: Schill
authors.forename: Georg
authors.initials: G
authors.lastname: Brabant
authors.forename: Andreas
authors.initials: A
authors.lastname: Schüring
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: Jörg
authors.initials: J
authors.lastname: Gromoll
authors.forename: Christof
authors.initials: C
authors.lastname: Schöfl
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D011085:Polycystic Ovary Syndrome / Q000235:genetics / Q000503:physiopathology*; D012150:Polymorphism, Restriction Fragment Length; D011944:Receptors, Androgen / Q000235:genetics*; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid; D013739:Testosterone / Q000097:blood / Q000502:physiology*
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone