TY - JOUR
T1 - A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity
AU - Kevenaar, Marlies E.
AU - Themmen, Axel P.N.
AU - Rivadeneira, Fernando
AU - Uitterlinden, André G.
AU - Laven, Joop S.E.
AU - van Schoor, Natasja M.
AU - Lips, Paul
AU - Pols, Huibert A.P.
AU - Visser, Jenny A.
PY - 2007/9
Y1 - 2007/9
N2 - 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.
AB - 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.
KW - Anti-Müllerian hormone
KW - Follicle recruitment
KW - Menopause
KW - Polymorphism
UR - http://www.scopus.com/inward/record.url?scp=34548082482&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/humrep/dem176
DO - https://doi.org/10.1093/humrep/dem176
M3 - Article
C2 - 17636279
SN - 0268-1161
VL - 22
SP - 2382
EP - 2388
JO - Human Reproduction
JF - Human Reproduction
IS - 9
ER -