A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity.
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 Ile(49)Ser 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.
Kevenaar
Marlies E
ME
Department of Internal Medicine, Room Ee532, PO Box 2040, Erasmus MC, 3000 CA Rotterdam, The Netherlands. m.kevenaar@erasmusmc.nl
Themmen
Axel P N
AP
Rivadeneira
Fernando
F
Uitterlinden
André G
AG
Laven
Joop S E
JS
van Schoor
Natasja M
NM
Lips
Paul
P
Pols
Huibert A P
HA
Visser
Jenny A
JA
D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007532:Isoleucine / Q000737:chemistry / Q000235:genetics; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D009426:Netherlands; D018000:Receptors, Peptide / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012694:Serine / Q000737:chemistry / Q000235:genetics
D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D007532:Isoleucine; D012694:Serine