A functional anti-Mullerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients

Marlies Kevenaar, Joop Laven, Sharon Lie Fong, André Uitterlinden, Frank Jong, Axel Themmen, Jenny Visser

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Context: 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-Mullerian 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. Design: 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. Setting/Subjects: A total of 331 women with PCOS, 32 normoovulatory controls, and 3635 population-based controls were included. Main Outcome Measures: 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 -482A>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 49Ser 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 theAMHIle49Ser polymorphism contributes to the severity of the PCOS phenotype.
Original languageUndefined/Unknown
Pages (from-to)1310-1316
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
Publication statusPublished - 2008

Research programs

  • EMC MM-01-39-02
  • EMC MM-01-39-04
  • EMC MM-01-52-07

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