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

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.

Keywords: Arg72Pro variant; allele frequencies; genotyping; inheritance models; recurrent pregnancy loss.