title: FSHB-211 and FSHR 2039 are associated with serum levels of follicle-stimulating hormone and antimüllerian hormone in healthy girls: a longitudinal cohort study.
abstract: OBJECTIVE
  To investigate whether genetic polymorphisms in the FSH pathway (FSHB-211 G→T and FSHR 2039 A→G) affect serum levels of FSH, antimüllerian hormone (AMH), and age at pubertal onset. FSH secretion and FSH signal transduction are enhanced in carriers of FSHB GG and FSHR AA, respectively. Furthermore, the combined genotype FSHB GG+FSHR AA is the most favorable for male gonadal function, but the effect of this genotype has never been evaluated in peripubertal females. AMH is a marker of ovarian function and is negatively correlated with FSH in prepubertal girls.
  
  
  METHODS
  Secondary analyses of a prospective cohort study.
  
  
  METHODS
  General community.
  
  
  METHODS
  We examined 78 healthy girls twice yearly for 6 years; the median age at baseline was 9.3 years.
  
  
  METHODS
  None.
  
  
  METHODS
  Hormone levels were measured by immunoassays, and DNA was isolated from blood and genotyped by restriction fragment length polymorphism of polymerase chain reaction-amplified regions.
  
  
  RESULTS
  Carriers of FSHB GG+FSHR AA had higher FSH before pubertal onset (median 2.2 vs. 1.5 IU/L) and lower AMH (13.8 vs. 19.4 pmol/L) compared with carriers of other genotypes. In crude analysis, girls with FSHB GG+FSHR AA entered puberty earlier, 9.7 vs. 10.6 years. However, the difference was no longer statistically significant after including interval-, right-, and left-censored data in a probit analysis.
  
  
  CONCLUSIONS
  The combined effect of FSHB GG+FSHR AA may potentiate the FSH pathway, which increases serum levels of FSH and reduces AMH. Common variations in genes regulating follicle growth may affect AMH levels independently of the number of resting primordial follicles.
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, Faculty of Health and Medical Science, University of Copenhagen, Denmark. Electronic address: casperhagen@gmail.com.
authors.forename: Casper P
authors.initials: CP
authors.lastname: Hagen
authors.forename: Lise
authors.initials: L
authors.lastname: Aksglaede
authors.forename: Kaspar
authors.initials: K
authors.lastname: Sørensen
authors.forename: Annette
authors.initials: A
authors.lastname: Mouritsen
authors.forename: Mikkel G
authors.initials: MG
authors.lastname: Mieritz
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.forename: Jørgen Holm
authors.initials: JH
authors.lastname: Petersen
authors.forename: Kristian
authors.initials: K
authors.lastname: Almstrup
authors.forename: Ewa
authors.initials: E
authors.lastname: Rajpert-De Meyts
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
mesh_terms: D000293:Adolescent; D000367:Age Factors; D054304:Anti-Mullerian Hormone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D003718:Denmark; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood* / Q000235:genetics*; D037201:Follicle Stimulating Hormone, beta Subunit / Q000097:blood* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007118:Immunoassay; D008137:Longitudinal Studies; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011627:Puberty / Q000097:blood / Q000235:genetics; D011962:Receptors, FSH / Q000235:genetics*
chemical_list: D015415:Biomarkers; D043373:Follicle Stimulating Hormone, Human; D037201:Follicle Stimulating Hormone, beta Subunit; D011962:Receptors, FSH; D054304:Anti-Mullerian Hormone
keywords: AMH; FSH; FSHB; FSHB-211 G→T; FSHR; FSHR 2039 A→G; puberty