The TP73 gene polymorphism (rs4648551, A>G) is associated with diminished ovarian reserve

PLoS One. 2015 Mar 20;10(3):e0120048. doi: 10.1371/journal.pone.0120048. eCollection 2015.


It's known that the members of the TP53 family are involved in the regulation of female reproduction. Studies in mice showed that the TP73 gene (member of this family) plays a role in the size of follicular pool, ovulation rate and maintenance of genomic stability. In the present study we analyzed data from 605 patients with ≤ 37 years attending their first intracytoplasmic sperm injection (ICSI). The association between the TP73 polymorphism (rs4648551, A>G) and the following parameters related to ovarian reserve, like age, antral follicular count (AFC), anti-Mullerian hormone levels (AMH) and ovarian response prediction index (ORPI) was evaluated. Our results showed an association of the AA genotype with diminished ovarian reserve (AMH <1, AFC ≤9). Women presenting the AA genotype had a 2.0-fold increased risk for having AMH <1 and AFC ≤9 (OR 2.0, 95% CI 1.23-3.31, P = 0.005). Patients presenting AA genotype had the lowest levels of AMH (P = 0.02), the lowest number of antral follicles (P = 0.01) and the lowest ORPI (P = 0.007). Analyzing the alleles, we can see an enrichment of the A allele in the group of diminished ovarian reserve (OR 1.4, 95%CI 1.02-1.83, P = 0.04). To the best of our knowledge, the present study is the first to analyze this polymorphism in humans for assessing the numbers of ovarian follicles and AMH levels and, therefore, the ovarian reserve. Our findings can contribute to the use of this polymorphism as a potential marker of diminished ovarian reserve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles*
  • Anti-Mullerian Hormone / blood
  • Brazil
  • Case-Control Studies
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies*
  • Genotype
  • Humans
  • Nuclear Proteins / genetics*
  • Ovarian Follicle
  • Ovarian Reserve / genetics*
  • Ovary
  • Ovulation Induction
  • Polymorphism, Single Nucleotide*
  • Tumor Protein p73
  • Tumor Suppressor Proteins / genetics*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • p73 protein, human
  • Anti-Mullerian Hormone

Grant support

This research was supported by Merck Serono grant (GFI-2014-16). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.