The association of CGG repeats in the FMR1 gene and timing of natural menopause  

Oleh:

Voorhuis, M. ; Onland-Moret, N.C. ; Fauser, B.C.J.M. ; Amstel, H.K. Ploos van ; Schouw, Y.T. van der ; Broekmans, F.J.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 28 no. 02 (Feb. 2013), page 496-501.
Topik: age at menopause ; FMR1 gene ; CGG repeats ; fragile X ; ovarian ageing

Ketersediaan

Perpustakaan FK Nomor Panggil: H07.K.2013.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

STUDY QUESTION Is there an association between the number of CGG repeats in the FMR1 gene in the normal and intermediate range and age at natural menopause? SUMMARY ANSWER The number of CGG repeats in the normal and intermediate range in the FMR1 gene was not associated with age at natural menopause. WHAT IS KNOWN ALREADY Excessive triple CGG repeats in the FMR1 gene have been widely associated with primary ovarian insufficiency. Recently, the number of CGG repeats in the normal and intermediate range (up to 55 repeats) was found to be associated with serum levels of anti-Müllerian hormone and follicle-stimulating hormone, as markers for ovarian ageing. This suggests that repeats in the normal and intermediate range could be involved in the rate of exhaustion of the ovarian primordial follicle pool and ultimately the timing of menopause. STUDY DESIGN, SIZE Cross-sectional study in a population-based sample of 3611 Caucasian women with natural menopause. PARTICIPANTS/MATERIALS, SETTING, METHODS The FMR1 CGG repeat number was determined by PCR amplification in 3611 women with a known age at natural menopause. A possible relation between CGG repeats in the normal and intermediate range (up to 55 repeats) and menopausal age were analysed in various ways, including linear regression analysis and analysis of variance. MAIN RESULTS AND THE ROLE OF CHANCE The number of CGG repeats in the normal and intermediate range in the FMR1 gene was not associated with age at natural menopause. The mean age at menopause was 50.30 (±4.2) years for women with <45 repeats and 50.64 (±3.4) years for women with intermediate-sized repeats (P = 0.37). Linear regression analysis of the number of CGG repeats showed no association with menopausal age (ß = 0.019, P = 0.16). LIMITATIONS, REASONS FOR CAUTION In our cohort, age at menopause was self-reported and determined retrospectively. WIDER IMPLICATIONS OF THE FINDINGS Earlier observations suggesting that the number of CGG repeats in the normal and intermediate range is associated with the individual variation of the ovarian ageing process could not be confirmed in the current, large sample size study. A relation between the number of CGG repeats in the normal and intermediate range and age at natural menopause appeared to be absent. This finding questions the role of CGG repeat sizes in the ovarian ageing process. STUDY FUNDING/COMPETING INTEREST(S) N.C.O.-M., Y.T.S. and H.K.P.A. have nothing to declare. M.V. is financially supported by a grant from the Dutch Organisation for Scientific Research (NWO). F.J.B. is a member of the external advisory board for Merck Serono, The Netherlands, and does consultancy work for MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order); Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. TRIAL REGISTRATION NUMBER Not applicable.

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