title: The significance of fragile X mental retardation gene 1 CGG repeat sizes in the normal and intermediate range in women with primary ovarian insufficiency.
abstract: OBJECTIVE
  Are fragile X mental retardation gene 1 (FMR1) CGG repeats in the normal and intermediate range (up to 55 repeats) associated with primary ovarian insufficiency (POI) in a large case-control study?
  
  
  CONCLUSIONS
  No association was found between CGG repeats of intermediate size and POI compared with controls.
  
  
  BACKGROUND
  CGG repeats in the FMR1 gene in the premutation range (55-200 repeats) have consistenly associated with POI. Intermediate range CGG repeats have been considered for a potential association with POI.
  A case-control study in 375 well-phenotyped Dutch women diagnosed with POI and 3368 controls with natural menopause ≥40 years of age.
  
  
  METHODS
  The FMR1 CGG repeat number was determined by PCR amplification in women diagnosed with POI and women with a known age at natural menopause ≥40 years. The prevalence of intermediate sized CGG repeats (45-54 repeats) was compared between POI cases and controls using Fisher's exact test. Differences in mean CGG repeat lengths on allele 1 and allele 2 between POI cases and controls were tested using analysis of variance.
  
  
  RESULTS
  The frequency of intermediate sized CGG repeats on the allele with the longest triple repeat number was not statistically significantly different between POI cases and controls (2.7 and 3.8%, respectively, odds ratio 0.72, 95% confidence interval: 0.38-1.39, P = 0.38). In women with POI, linear regression analysis for age at POI diagnosis and CGG repeat size also failed to show any association (β = -0.018, P = 0.74).
  
  
  CONCLUSIONS
  FMR1 CGG repeat lengths in POI cases and controls were genotyped in two different laboratories. The distributions of CGG repeats may vary among the different ethnic populations in our study. Also, in our study women with primary amenorrhea (N = 17) were included in the POI group.
  
  
  CONCLUSIONS
  We found no association between intermediate sized CGG repeats and POI compared with controls. Therefore, a role for FMR1 CGG repeat sizes up to 55 repeats in the ovarian ageing process may be questioned. Moreover, there seems limited value in the evaluation of normal- and intermediate FMR1 repeat size in the diagnostic work-up of women affected by POI, or for prognostic purposes in women at risk of developing POI.
  
  
  BACKGROUND
  The Prospect-EPIC study was funded by 'Europe Against Cancer' Program of the European Commission (SANCO); the Dutch Ministry of Health; the Dutch Cancer Society; ZonMW the Netherlands Organization for Health Research and Development; World Cancer Research Fund (WCRF) and the Dutch Heart Association.
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands m.voorhuis@umcutrecht.nl.
authors.forename: M
authors.initials: M
authors.lastname: Voorhuis
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: N C
authors.initials: NC
authors.lastname: Onland-Moret
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Janse
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: H K
authors.initials: HK
authors.lastname: Ploos van Amstel
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Goverde
authors.affiliation: Department of Obstetrics and Gynaecology, VU Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: C B
authors.initials: CB
authors.lastname: Lambalk
authors.affiliation: Department of Reproductive Medicine, Erasmus Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: J S E
authors.initials: JS
authors.lastname: Laven
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Y T
authors.initials: YT
authors.lastname: van der Schouw
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: F J M
authors.initials: FJ
authors.lastname: Broekmans
authors.affiliation: Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: B C J M
authors.initials: BC
authors.lastname: Fauser
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D016017:Odds Ratio; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D011379:Prognosis; D019680:Trinucleotide Repeat Expansion; D018911:Trinucleotide Repeats; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: CGG repeats; fragile X mental retardation gene 1; menopause; ovarian ageing; primary ovarian insufficiency