FP11-1 CYP19A1 and PPARG Methylation Associated with Pubertal Timing in Young Girls

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP11-Pediatric Endocrinology
Clinical
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:00 AM
Room 104 (Moscone Center)

Poster Board SAT-596
Theresa Ryan Stueve*1, Mary Snow Wolff2, Susan Teitelbaum2, Ashley Pajak2 and Jia Chen2
1Keck School of Medicine at the University of Southern California, Los Angeles, CA, 2Mount Sinai School of Medicine, NY, NY
Background and Significance: Early puberty is an intermediate risk factor for later reproductive and metabolic disorders including breast cancer and diabesity1. DNA methylation patterns in genes related to hormone and adipose metabolism, such as CYP19A1 (aromatase)2 and PPARG (PPAR-gamma) are associated with altered gene expression which may contribute to pathogenesis of these diseases. If present in early life, it is conceivable these same methylation aberrations may result in hormone perturbations that alter puberty timing. 

Objective and Method: We used Cox proportional hazard models to investigate whether promoter DNA methylation of CYP19A1 and PPARG, independently or in concert with body mass index (BMI), was associated with age at  pubic hair development (PH2) or breast development (B2) in a cohort of 6-8 year-old Black and Hispanic New York City girls (n=125) who were between 6-8 years-old at enrollment. Percent methylation of specific CpG dinucleotides in these promoters was quantified in buccal DNA by bisulfite pyrosequencing. Overweight was defined as BMI greater than or equal to the 85t h percentile for age.  

Results: An inverse association between CYP19A1 and PH2 was suggested (HR = 0.95, CI= 0.90-1.00, p = 0.05).  CYP19A1 methylation was not independently associated with breast development, but appeared to modify timing of B2 when BMI was considered (BMI-CYP19A1 interaction p = 0.085). Specifically, compared to normal weight girls with ‘high’ CYP191A1 methylation (reference), overweight girls with ‘low’ CYP191A1 methylation had a higher risk of early B2 (HR = 2.15; 95% CI= 1.23- 3.76). Similar trends were suggested for PH2 when CYP19A1 and BMI were considered together, but were not statistically significant. No significant associations between PPARG and pubertal development were detected.

Conclusion: Our findings suggest the DNA methylation status of a specific CYP19A1 promoter may influence timing of breast development in overweight girls. Consistent with other emerging reports, these observations indicate epigenetic biomarkers of risk may be identified in non-invasively collected surrogate tissues.

1. Sloboda DM, Hart R, Doherty DA, Pennel CE, and Hickey M. (2006). Age at menarche: Influences of prenatal and postnatal growth.     The Journal of Clinical Endocrinology and Metabolism, 92(1), 46-50. 2. Demura, M and Bulun, SE. (2008).  CpG dinucleotide methylation of the CYP19 I.3/II promoter modulates cAMP- stimulated aromatase     activity. Molecular and Cellular Endocrinology. 283 (1–2)1 27–132. 3. Fujiki K, Kano F, Shiota K, and Murata M. (2009). Expression of the peroxisome proliferator activated receptor γ gene is repressed by       DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol; 7: 38.

Nothing to Disclose: TRS, MSW, ST, AP, JC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Acknowledgements: This work was made possible by the Breast Cancer and the Environment Research Program (BCERP) award numbers U01ES012771, U01ES019454 and U01ES019457 from the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI), and CSTA-UL1RR029887 from the National Center for Research Resources (NCRR).  Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NCI, or the National Institutes of Health.
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