Prevalence and Genetic Association of the Prothrombin F2 G20210A Variant in Libyan Women with Unexplained Recurrent Pregnancy Loss: A Preliminary Case-Control Study

Abstract

Recurrent pregnancy loss (RPL) is a common gestational complication. The prothrombin F2 G20210A (rs1799963) variant has been implicated in placental vascular thrombosis that triggers RPL; however, its prevalence and clinical relevance remain unstudied among Libyan women. This investigation evaluated the prevalence and genetic association of the F2 G20210A variant with unexplained RPL in Libya. This preliminary case-control study enrolled 66 Libyan women, comprising 56 cases with unexplained RPL (≥ 2 consecutive losses before 24 weeks of gestation) and 10 healthy controls (≥ 2 full-term live births; no history of pregnancy loss). Genotyping was performed using the Sacace FII Prothrombin Real-Time PCR Kit. Statistical analyses utilized Fisher’s exact and Chi-square (χ²) tests. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated using Haldane’s continuity correction, designating wild-type categories as reference. The prevalence of the F2 G20210A variant among cases was 10.7% (6/56), presenting exclusively as heterozygous (GA); the homozygous mutant (AA) genotype was absent (0.0%) in both groups. The wild-type GG genotype was present in 89.3% (n = 50) of cases and 100.0% (n = 10) of controls. The mutant A allele frequency was 5.7% in cases and 0.0% in controls. Both the case (p = 0.673) and control (p = 1.000) cohorts conformed to Hardy-Weinberg equilibrium. Under a dominant model of inheritance (GA+AA vs GG), no statistically significant association was observed between the variant and RPL risk at the genotype (OR = 2.70, 95% CI: 0.14 ̶ 51.52, p = 0.580) or allele (OR = 2.50, 95% CI: 0.14 ̶ 45.74, p = 0.590) level. Internal case cohort analysis revealed significant clustering of early first-trimester losses (92.9%, n = 52; p < 0.0001) and parental consanguinity (71.4%, n = 40; p = 0.0013). This first genetic screening of the F2 G20210A variant in Libya identified a 10.7% carrier rate among RPL cases without a statistically significant disease association. Consequently, routine molecular screening for F2 G20210A cannot be recommended as a standalone diagnostic marker for clinical gynecological practice based on these preliminary data. Larger, well-balanced cohort studies are required to establish a definitive national baseline prevalence. Ultimately, incorporating comprehensive multi-gene thrombophilic panels alongside advanced cytogenetic and genomic sequencing will be critical to fully clarify the complex etiology of RPL in Libya.