Associations of Polymorphisms in Anti-Müllerian Hormone (AMH Ile49Ser) and its Type II Receptor (AMHRII -482 A>G) on Reproductive Outcomes and Polycystic Ovary Syndrome: a Systematic Review and Meta-Analysis

Cell Physiol Biochem. 2016;39(6):2249-2261. doi: 10.1159/000447918. Epub 2016 Nov 7.


Background/aims: Reported associations of reproductive outcomes (RO) and polycystic ovary syndrome (PCOS) with genotypes of the Ile49Ser and -482A>G polymorphisms in the Anti-Müllerian hormone (AMH) gene and its type II receptor (AMHRII), respectively, have conflicting results.

Methods: PubMed, Google Scholar and Science Direct databases were searched for studies that investigated Ile49Ser and -482A>G in RO and PCOS. Using the metaanalytic approach, we estimated risk (odds ratio [OR] with 95% confidence intervals) using standard genetic models.

Results: All calculated summary effects were non-significant. Overall associations of Ile49Ser and -482A>G with RO were absent (OR 0.95-0.99, P = 0.76-0.96) but implied increased risk in PCOS (OR 1.07-1.17, P = 0.49-0.55). Where heterogeneity of the pooled ORs were present, its sources were explored using the Galbraith plot. Detection and omission of the outlying studies in both polymorphisms not only erased heterogeneity of the recalculated pooled outcomes but also changed direction of association, where null effects turned to increased risk (Ile49Ser in RO) and increased risk became reduced risk (-482A>G in PCOS). Implications of the Ile49Ser and -482A>G, effects pointed to protection for Caucasians (OR 0.64-0.89, P = 0.36-0.73) in RO and increased risk in PCOS (OR 1.19-1.45, P = 0.28-0.65). Asian effects in RO and PCOS were variable (OR 0.97-1.24, P = 0.58-0.91).

Conclusions: In summary, we found no evidence of significant associations of Ile49Ser and -482A>G with RO and PCOS, although contrasting Ile49Ser effects were implied among Caucasians between RO (up to 0.36% reduced risk) and PCOS (up to 1.5-fold increased risk).

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-Mullerian Hormone / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease*
  • Humans
  • Models, Genetic
  • Polycystic Ovary Syndrome / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Peptide / genetics*
  • Receptors, Transforming Growth Factor beta / genetics*
  • Reproduction / genetics*


  • Receptors, Peptide
  • Receptors, Transforming Growth Factor beta
  • anti-Mullerian hormone receptor
  • Anti-Mullerian Hormone