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Association between TP53 Arg72Pro variant and recurrent pregnancy loss in the Greek population

  • Dimitra Dedousi , Despoina Mavrogianni , Myrto Papamentzelopoulou ORCID logo EMAIL logo , Sofoklis Stavros ORCID logo , Rami Raouasnte , Dimitris Loutradis and Peter Drakakis
Published/Copyright: July 4, 2022

Abstract

Objectives

The present case-control study investigates whether TP53 Arg72Pro variant (rs1042522) serves as a risk factor for recurrent pregnancy loss (RPL) in Greek women.

Methods

The study group consisted of 100 patients with at least two miscarriages of unexplained etiology, before the 24th week of gestation. The control group included 106 women with no pregnancy loss history. DNA was extracted and genotyped using specific primers for PCR amplification of the Arg72 and Pro72 alleles. Sanger sequencing was used for the discrimination between heterozygotes and homozygotes for Arg72Pro variant.

Results

This is the first study demonstrating the statistically significant higher frequency of TP53 Arg72Pro variant in Greek RPL women compared to controls (38% vs. 6.6%; OR=8.6682, 95% CI: 3.6446–20.6160; p<0.0001). GC genotype (Arg/Pro) and CC genotype (Pro/Pro) were statistically more common in RPL patients than in controls (16% vs. 1.9%; p=0.0027, and 22 vs. 4.7%; p=0.0008, respectively). C allele frequency was statistically significant higher in RPL group than in controls (30.0 vs. 5.7%; p<0.0001). According to the inheritance mode analysis, the model that best fit the data was the dominant model (OR=8.67, 95% CI=3.64–20.62; p<0.0001).

Conclusions

The is the first study disclosing strong evidence that TP53 rs1042522 is significantly associated with a higher risk for recurrent pregnancy loss in Greek women following a dominant model, thus, serving as a genetic marker for identifying women at increased risk of recurrent miscarriages.


Corresponding author: Dr. Myrto Papamentzelopoulou, Molecular Biology Unit, Division of Human Reproduction, 1st Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, 80, Vasilissis Sofias Ave., 11528, Greece, Phone: +30 2132162627, Fax: +30 2132162898, E-mail:

Acknowledgments

We would like to acknowledge the contribution of all recruited patients in the present study.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2021-11-13
Accepted: 2022-06-11
Published Online: 2022-07-04

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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