Thrombophilia-Related Single Nucleotide Variants and Altered Coagulation Parameters in a Cohort of Mexican Women with Recurrent Pregnancy Loss

Background: Recurrent pregnancy loss (RPL) is a multifactorial condition in which genetic variants associated with thrombophilia may contribute to altered coagulation and adverse pregnancy outcomes. Objective: This study aimed to investigate the association between thrombophilia-related single nucleotide variants (SNVs) and coagulation-related metabolites in a cohort of Mexican women with RPL. Methods: A retrospective and descriptive design was conducted including 105 women with at least two consecutive miscarriages and with a multidisciplinary approach that included a thrombophilia-associated SNVs panel. Peripheral blood samples were collected after fasting for biochemical and molecular analyses. Genotyping of thrombophilia-associated SNVs was performed using real-time PCR with custom-designed TaqMan probes on a Rotor-Gene Q platform, including variants in AGT (rs4762, rs699), F7 (rs6046), FGB (rs1800790), MTR (rs1805087), MTRR (rs1801394), MTHFR (rs1801133, rs1801131), F2 (rs1799963), F5 (rs6025), SERPINE1 (rs1799889), F12 (rs1801020), and F13A1 (rs5985) genes. Coagulation parameters evaluated were folic acid, cobalamin, fibrinogen, D-dimer, homocysteine, antithrombin III activity, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and Factor XII activity. Results: Significant differences were found in INR values across F7-rs6046 genotypes (p = 0.006), with an additive model showing a mean difference of 0.05 (p = 0.0009). The F12-rs1801020 variant was strongly associated with Factor XII activity (p = 0.002) and aPTT (p = 0.045). Conclusions: These findings indicate that F7-rs6046 and F12-rs1801020 genotypes influence specific coagulation parameters, suggesting that certain thrombophilia-associated SNVs may modulate the hemostatic profile in Mexican women with RPL and contribute to personalized risk assessment in reproductive medicine.