A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity

Marlies E. Kevenaar*, Axel P.N. Themmen, Fernando Rivadeneira, André G. Uitterlinden, Joop S.E. Laven, Natasja M. van Schoor, Paul Lips, Huibert A.P. Pols, Jenny A. Visser

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment in the mouse ovary. We hypothesize that in women AMH signaling also regulates the usage of the primordial follicle pool and hence influences the onset of menopause. Since age at menopause has a strong genetic component, we investigated the role of AMH signaling using a candidate gene approach. Methods: In two large population-based cohorts of Dutch post-menopausal women (n = 2381 and n = 248), we examined the association between two polymorphisms, one in the AMH gene and one in the AMH type II receptor (AMHR2) gene, and natural age at menopause. Results: The AMH Ile49Ser polymorphism (rs10407022) was not associated with age at menopause in either cohort. In the Rotterdam cohort, the AMHR2 -482 A > G polymorphism (rs2002555) was associated with age at menopause in interaction with the number of offspring (P = 0.001). Nulliparous women homozygous for the G-allele entered menopause 2.6 years earlier compared with nulliparous women homozygous for the A-allele (P = 0.005). In the LASA cohort, women with the G/G genotype tended to enter menopause 2.8 years earlier compared with the A/A genotype (P = 0.063). Conclusions: The observed association of the AMHR2 -482 A > G polymorphism with natural age at menopause suggests a role for AMH signaling in the usage of the primordial follicle pool in women.

Original languageEnglish
Pages (from-to)2382-2388
Number of pages7
JournalHuman Reproduction
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 2007

Cite this

Kevenaar, M. E., Themmen, A. P. N., Rivadeneira, F., Uitterlinden, A. G., Laven, J. S. E., van Schoor, N. M., ... Visser, J. A. (2007). A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity. Human Reproduction, 22(9), 2382-2388. https://doi.org/10.1093/humrep/dem176