A functional anti-mullerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients.
BACKGROUND
The common characteristic of polycystic ovary syndrome (PCOS) is a disturbance in the selection of the dominant follicle, resulting in anovulation. In PCOS women, serum anti-Müllerian hormone (AMH) levels are elevated. Because AMH decreases FSH sensitivity in mice, the elevated AMH levels may contribute to the disturbed follicle selection in PCOS women.


OBJECTIVE
The objective of the study was to investigate the role of the AMH signaling pathway in the pathophysiology of PCOS using a genetic approach.


METHODS
The association of the AMH Ile(49)Ser (rs10407022) and the AMH type II receptor -482 A>G (rs2002555) polymorphism with PCOS susceptibility and phenotype was studied in a large cohort of PCOS women.


METHODS
A total of 331 women with PCOS, 32 normoovulatory controls, and 3635 population-based controls were included.


METHODS
Ovarian parameters, serum AMH, FSH, androgen, and estradiol levels were measured.


RESULTS
Genotype and allele frequencies for the AMH Ile(49)Ser and AMH type II receptor -482 A>G polymorphism were similar in PCOS women and controls. However, within the group of PCOS women, carriers of the AMH (49)Ser allele less often had polycystic ovaries (92.7 vs. 99.5%, P = 0.0004), lower follicle numbers (P = 0.03), and lower androgen levels, compared with noncarriers (P = 0.04). In addition, in vitro studies demonstrated that the bioactivity of the AMH (49)Ser protein is diminished, compared with the AMH (49)Ile protein (P < 0.0001).


CONCLUSIONS
Genetic variants in the AMH and AMH type II receptor gene do not influence PCOS susceptibility. However, our results suggest that the AMH Ile(49)Ser polymorphism contributes to the severity of the PCOS phenotype.
Kevenaar
Marlies E
ME
Department of Internal Medicine, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
Laven
Joop S E
JS
Fong
Sharon Lie
SL
Uitterlinden
André G
AG
de Jong
Frank H
FH
Themmen
Axel P N
AP
Visser
Jenny A
JA
D000328:Adult; D000728:Androgens / Q000097:blood*; D000818:Animals; D054304:Anti-Mullerian Hormone / Q000097:blood / Q000235:genetics*; D002460:Cell Line; D005260:Female; D005838:Genotype; D006801:Humans; D051379:Mice; D006080:Ovarian Follicle / Q000473:pathology*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D018000:Receptors, Peptide / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics
D000728:Androgens; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone