Correlation of TP53 (rs1625895), TP73 (rs3765730), MMP9 (rs17576), and MTHFR (rs868014) polymorphisms with low ovarian reserve

Abstract

Objective:To investigate the influence of the Single Nucleotide Polymorphisms (SNPs) TP53 rs1625895, TP73 rs3765730, MMP9 rs17576, and MTHFR rs868014 on ovarian reserve (OR) in infertile patients. Study design:A prospective cross-sectional study was carried out in 145 infertile women. The patients were divided into two groups according to ovarian reserve, characterized by association between AMH levels and AFC:-Group I: 86 patients defined as having low OR (LOR) by AMH < 1 ng/mL + AFC ≤ 9.-Group II: 59 patients defined as having normal OR (NOR) by AMH > 2 ng/mL + AFC ≥ 15.After patient distribution, both groups were compared (LOR X NOR) regarding the genotypes of the SNPs TP53 T/C rs1625895, TP73 G/A rs3765730, MMP9 Gln/Arg rs17576, and MTHFR A/G rs868014. Result(s):The frequency of the TP53-T/T genotype was greater in the LOR and the TP53-C/C genotype was more frequent in patients with NOR. This association was confirmed by the frequency of alleles, where the presence of the T allele was significantly higher in patients who exhibited LOR (P = 0.0003). The frequency of the TP73-G/G genotype and of the G allele was higher in the LOR group (P = 0.01). Considering the MMP9 gene, the frequency of the Gln/Gln genotype was higher in the LOR group. However, the Gln/Arg genotype and the Arg allele prevailed in the NOR group (P = 0.006). The frequency of the MTHFR-A/A genotype was higher in the LOR group, whereas that of the MTHFR-GG genotype was higher in the NOR group. The presence of allele A was significantly higher in the LOR group (P = 0.002). The regression analysis shows that patients who present the TP53-T/T, TP73-G/G, MMP9-Gln/Gln, and MTHFR-A/A genotypes are 3.6X, 3.1X, 3.2X, and 3.7X more likely of having LOR, respectively. In addition, the association of the TP53/TT + TP73/GG genotypes increased the chance of women being included in the LOR group in 5.7-fold. Conclusion(s):The genotypes TP53-T/T, TP73-G/G, MMP9-Gln/Gln, and MTHFR-A/A increase the chance of women to exhibit LOR. These polymorphisms could be useful as genetic markers of low ovarian reserve in infertile patients.