OR37-6 FSHB –211 and FSHR 2039 polymorphisms affect FSH and AMH levels in healthy girls: a longitudinal cohort study

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR37-Pediatric Endocrinology: HPG Axis Disorders
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 12:30 PM
Room 102 (Moscone Center)
Casper P. Hagen*1, Lise Aksglaede1, Kaspar Sørensen1, Annette Mouritsen1, Mikkel Grunnet Mieritz1, Katharina M Main1, Jørgen Holm Petersen1, Kristian Almstrup1, Ewa Rajpert-De Meyts1, Richard Alexander Anderson2 and Anders Juul1
1Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 2Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom
Context: Genetic polymorphisms in the promoter of the FSH beta subunit (FSHB –211 G>T) and in the gene encoding the FSH receptor (FSHR 2039 A>G) affect the potency of the FSH pathway. Male carriers of FSHB GG+FSHR AA have the most favourable gonadal function, but the effect of this combination of genotypes has never been evaluated in females. AMH is a marker of ovarian function and is negatively correlated with FSH in prepubertal girls. As increasing levels of circulating gonadotropins induce puberty, FSHB and FSHR may influence serum levels of FSH and AMH, as well as age at pubertal onset.

Objective: To investigate the associations between genetic polymorphisms (FSHB and FSHR) and serum levels of FSH, AMH, and age at pubertal onset.

Design and Setting: We examined 78 healthy girls twize year for 5 years; median age at baseline 9.3 years. Hormone levels were measured by immunoassays and DNA was isolated from blood and genotyped by restriction fragment length polymorphism (RFLP) of PCR-amplified regions.

Results: Carriers of FSHB GG+FSHR AA had higher FSH prior to pubertal onset (median 2.2 vs. 1.5 IU/L, p=0.05) and lower AMH (13.8 vs. 19.4 pmol/L, p=0.04) compared with carriers of other genotypes. In crude analysis, girls with FSHB GG+FSHR AA entered puberty earlier; 9.7 vs. 10.6 years (p=0.03). However, the difference was no longer statistical significant after conservative probit analysis including interval-, right- and left-censored data.

Conclusions: The combined effect of FSHB GG+FSHR AA may potentiate the FSH-pathway, which increases FSH, reduces AMH, and possibly accelerates pubertal onset. Common variations in genes that regulate follicle growth, may affect AMH levels independently from the number of resting primordial follicles.

Disclosure: RAA: Consultant, Beckman-Coulter. Nothing to Disclose: CPH, LA, KS, AM, MGM, KMM, JHP, KA, ERDM, AJ

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

Sources of Research Support: The Copenhagen Puberty Study received financial support from the Danish Agency for Science, Technology and Innovation (09-067180), Kirsten and Freddy Johansen´s Foundation, Classenske Fideicommis´ Foundation, and Family Hede Nielsen Foundation.
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