FSHB -211 and FSHR 2039 polymorphisms are associated with serum levels of FSH, AMH and age of pubertal onset in 78 healthy girls: a longitudinal cohort study

Casper P Hagen; Lise Aksglaede; Kaspar Sorensen; Annette Mouritsen; Mikkel G Mieritz; Katharina M Main; Kristian Almstrup; Meyts Ewa Rajpert-De; Richard A Anderson; Anders Juul

doi:10.1530/endoabs.32.OC5.5

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Endocrine Abstracts (2013) 32 OC5.5 | DOI: 10.1530/endoabs.32.OC5.5

ECE2013 Oral Communications Reproduction (6 abstracts)

FSHB −211 and FSHR 2039 polymorphisms are associated with serum levels of FSH, AMH and age of pubertal onset in 78 healthy girls: a longitudinal cohort study

Casper P Hagen ¹ , Lise Aksglaede ¹ , Kaspar Sørensen ¹ , Annette Mouritsen ¹ , Mikkel G Mieritz ¹ , Katharina M Main ¹ , Kristian Almstrup ¹ , Ewa Rajpert-De Meyts ¹ , Richard A Anderson ² & Anders Juul ¹

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¹Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; ²Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

Context: Potency of the FSH-pathway varies according to polymorphisms in the promoter of the gene encoding the FSH beta subunit (FSHB −211 G>T, rs10835638) and in the gene encoding the FSH receptor (FSHR 2039 A>G, rs6166). A recent study suggested that carriers of the combination of FSHB GG and FSHR AA had the most reproductive ‘fit’ phenotype (higher serum FSH and a more sensitive FSH receptor). In pre-pubertal girls, FSH and AMH levels correlate negatively indicating a pituitary–gonadal set-point.

Objective: To evaluate if polymorphisms in FSHB and FSHR were associated with reproductive parameters in healthy girls.

Design and setting: Seventy-eight healthy girls were examined biannually in the COPENHAGEN Puberty Study; number of examinations per girl, median (range), 9 (2–13). Serum levels of hormones were measured by immunoassays. Genotyping was determined by PCR amplification followed by restriction enzymes specific for the genotypes (RFLP analysis).

Main outcome measures: Association analyses of single and combined polymorphisms with FSH, AMH, and age at pubertal onset.

Results: Carriers of (FSHB GG+FSHR AA) had higher levels of FSH prior to pubertal onset, lower mean serum levels of AMH, and they entered puberty earlier than girls with other combinations of genotypes; FSH 2.2 (1.3–3.9) vs 1.5 (0.4–4.4) IU/l (P=0.05), AMH 13.8 (5.6–53.9) vs 19.4 (4.8–47.4) pmol/l (P=0.04), and age of pubertal onset 9.7 (8.8–10.7) vs 10.6 (9.0–13.5) years (P=0.03), respectively.

Conclusions: Our findings indicate that genetic polymorphisms in the FSH pathway influence timing of puberty in healthy girls, as well as the pre-pubertal FSH-AMH set-point. Furthermore, it seems that individual AMH levels are determined by common variations in genes regulating follicle growth as well as the number of resting primordial follicles.