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Intermediate CGG repeat length at the FMR1 locus is not associated with hormonal indicators of ovarian age

Kline, Jennie K. PhD1,2,3; Kinney, Ann M. MPhil2; Levin, Bruce PhD4; Brown, Stephen A. MD5; Hadd, Andrew G. PhD6; Warburton, Dorothy PhD7

doi: 10.1097/GME.0000000000000139
Original Articles

Objective Premutation and intermediate CGG repeat length at the fragile X mental retardation 1 (FMR1) locus have been associated with premature ovarian failure. We tested whether intermediate length is associated with indicators of ovarian age in a sample of fertile women. Our primary measures of ovarian age were antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels.

Methods The cross-sectional sample comprised 258 women with karyotyped spontaneous abortions (140 trisomic spontaneous abortions and 118 chromosomally normal spontaneous abortions or spontaneous abortions with anomalies other than trisomy) and 325 women with recent live births (LBs). We analyzed data from the total sample and data from LBs only. We defined CGG repeat length by the length (both continuous and categorical) on the longer allele.

Results CGG repeat length was not significantly associated with either hormone measure. A repeat length of 35 to 54 CGG, versus the modal category of 30 CGG, was associated with an approximately 7% increase in median AMH level and a 3% increase in median FSH level. Results were unaltered when analyses were limited to LBs. Analyses of hormone levels using cutpoints to define older ovarian age showed no associations with repeat length. Among 10 women with repeat lengths of 35 to 54 CGG analyzed for AGG sequences, the uninterrupted CGG length was not significantly longer among women with hormonal indicators of “old” versus “young” ovarian age.

Conclusions Our data do not support an association between intermediate CGG repeat length and levels of AMH or FSH among fertile women.

From the 1Imprints Center, New York State Psychiatric Institute, New York, NY; 2Department of Epidemiology, 3Gertrude H. Sergievsky Center, and 4Department of Biostatistics, Columbia University, New York, NY; 5Department of Obstetrics, Gynecology, and Reproductive Science, The University of Vermont, Burlington, VT; 6Diagnostic Research and Technology Development, Asuragen Inc, Austin, TX; and 7Departments of Genetics and Development and Pediatrics, Columbia University, New York, NY.

Received August 12, 2013; revised and accepted September 25, 2013.

J.K.K. designed the study and analysis and wrote the manuscript. A.M.K. collaborated in study design and analysis, carried out statistical programming, and helped write the manuscript. B.L. collaborated in study design and analysis and helped write the manuscript. S.A.B. collaborated in the design of laboratory analyses and the assessment of validity and reliability, oversaw laboratory analyses for CGG repeat length, and helped write the manuscript. A.G.H. collaborated in the application of laboratory methods for assessing repeat length and in the assessment of the validity and reliability of the assay, oversaw analyses related to the structure of the repeat, and helped write the manuscript. D.W. collaborated in study design, oversaw the laboratory that karyotyped spontaneous abortion specimens, and helped write the manuscript.

Funding/support: Data collection for the New York study was supported by a grant (R01 AG 15386) from the National Institutes on Aging. Data collection for the New Jersey study was supported by a grant (R01 HD 42725) from the National Institutes on Child Health and Development. The work for this article, including CGG repeat length and hormone assays, was supported by a grant (R01 HD 053814-01A2) from the National Institutes on Child Health and Human Development. Funding for reagents was supported in part by a grant (R44 HD 066953 to Asuragen Inc) from the National Institutes on Child Health and Human Development.

Financial disclosure/conflicts of interest: None reported.

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Address correspondence to: Jennie K. Kline, PhD, Department of Epidemiology, Columbia University, Room 1607, 722 West 168th Street, New York, NY 10032. E-mail:

© 2014 by The North American Menopause Society.