title: Analysis of multiple data sets reveals no association between the insulin gene variable number tandem repeat element and polycystic ovary syndrome or related traits.
abstract: BACKGROUND
  Variation at the insulin gene VNTR (variable number tandem repeat) minisatellite has been reported to be associated with polycystic ovary syndrome (PCOS), but findings have been inconsistent and all studies have featured small sample sizes.
  
  
  OBJECTIVE
  To gain a robust understanding of the role of the INS-VNTR in PCOS susceptibility.
  
  
  METHODS
  Case-control, family-based association and quantitative trait analyses.
  
  
  METHODS
  A UK population comprising 255 parent-offspring trios, 185 additional cases, and 1062 control subjects (cases and controls all British/Irish) as well as 1599 women from a northern Finland population-based birth cohort characterized for PCO symptomatology and testosterone levels. VNTR class was inferred from genotyping of the -23HphI variant.
  
  
  METHODS
  None.
  
  
  METHODS
  INS-VNTR genotype frequencies between subject groups, body mass index, and testosterone levels by genotype.
  
  
  RESULTS
  Case-control analyses in both UK and Finnish samples failed to confirm previously reported class III allele associations with PCOS (UK, P = 0.43, Finnish, P = 0.31; Kruskal-Wallis chi2). Transmission analysis in trios showed no excess transmission of either allele (P = 0.62), regardless of parent of origin (maternal: P = 0.73; paternal: P = 0.66). No association between genotype and testosterone levels was seen in any sample (UK PCOS subjects, P = 0.95; Finnish symptomatic cases, P = 0.38; Finnish control women, P = 0.58).
  
  
  CONCLUSIONS
  Despite the strong biological candidacy and supportive data from previous studies, we conclude that variation at the INS-VNTR has no major role in the development of PCOS.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Powell
authors.forename: Lema
authors.initials: L
authors.lastname: Haddad
authors.forename: Amanda
authors.initials: A
authors.lastname: Bennett
authors.forename: Neda
authors.initials: N
authors.lastname: Gharani
authors.forename: Ulla
authors.initials: U
authors.lastname: Sovio
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Groves
authors.forename: Karen
authors.initials: K
authors.lastname: Rush
authors.forename: Micaela J
authors.initials: MJ
authors.lastname: Goh
authors.forename: Gerard S
authors.initials: GS
authors.lastname: Conway
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Hannu
authors.initials: H
authors.lastname: Martikainen
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.forename: Saara
authors.initials: S
authors.lastname: Taponen
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Halford
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Steve
authors.initials: S
authors.lastname: Franks
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008875:Middle Aged; D018598:Minisatellite Repeats; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D006113:United Kingdom
chemical_list: D007328:Insulin