title: Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor.
abstract: OBJECTIVE
  To characterize novel single-nucleotide polymorphisms (SNPs) in the human FSH receptor (FSHR) promoter region.
  
  
  METHODS
  Retrospective and basic research study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Women (202 from Germany and 55 from Indonesia) with male or tubal factor infertility undergoing controlled ovarian stimulation for IVF treatment.
  
  
  METHODS
  None.
  
  
  METHODS
  Frequency, distribution, and correlation with clinical data of the SNPs. Dual luciferase assays and electrophoretic mobility shift assays (EMSA).
  
  
  RESULTS
  We identified two SNPs and three mutations in the promoter region of the human FSHR which could be allocated to positions -29, -37, -114, -123, and -138 upstream of the translational initiation codon. One SNP showed a high incidence (-29: 44%, n = 202), but no correlation with basal FSH serum levels or ovarian response with the SNP at position -29 was found. Luciferase reporter assays, using pGL3 vector constructs, showed that mutations at positions -37 and -138 lead to significantly higher promoter activity. EMSA indicate that putative binding sites for transcription factors are affected by the SNPs.
  
  
  CONCLUSIONS
  The newly identified SNPs do not seem to influence clinical parameters substantially, but modulate expression of the FSHR via changes in transcription factor binding sites.
authors.affiliation: Institute of Reproductive Medicine, University Hospital, Münster, Germany.
authors.forename: Alain
authors.initials: A
authors.lastname: Wunsch
authors.forename: Yuni
authors.initials: Y
authors.lastname: Ahda
authors.forename: Ferya
authors.initials: F
authors.lastname: Banaz-Yaşar
authors.forename: Barbara
authors.initials: B
authors.lastname: Sonntag
authors.forename: Eberhard
authors.initials: E
authors.lastname: Nieschlag
authors.forename: Manuela
authors.initials: M
authors.lastname: Simoni
authors.forename: Jörg
authors.initials: J
authors.lastname: Gromoll
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D012189:Retrospective Studies
chemical_list: D043373:Follicle Stimulating Hormone, Human; D011962:Receptors, FSH