Department of Molecular Genetics, Al Borg Diagnostics, Jeddah, Kingdom of Saudi Arabia.
Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, 11432, Kingdom of Saudi Arabia.
Reprod Sci. 2023 Feb;30(2):656-666. doi: 10.1007/s43032-022-01063-1. Epub 2022 Aug 15.
Despite the fact that multiple recurrent pregnancy loss (RPL) etiologies have been identified, 50-70% of RPL cases remain enigmatic, and idiopathic RPL is still a serious medical challenge. A plethora of studies have investigated the correlation of RPL with variations in coagulation and/or fibrinolytic factors-encoding genes. Notwithstanding, evidence for a link between these variations and RPL remains discordant. We aimed to explore the association of thrombophilic and hypofibrinolytic gene variations with RPL development. Two hundred Saudi women were recruited in this study, comprising 150 women experiencing RPL and 50 healthy women. Thirteen genetic variants, including FV G1691A, FV A4070G, F2 G20210A, F13A1 G103T, FGB - 455G > A, PAI-1 - 675 4G/5G, ITGB3 T1565C, MTHFR C677T, MTHFR A1298C, ACE I/D, APOB G10708A, APOE T388C, and APOE C526T were genotyped using ViennaLab StripAssay. Women experiencing RPL harbor significantly higher frequencies of the F13A1 103 T, FGB - 455A, and ITGB3 1565C alleles than control women (p < 0.001). No differences in the prevalence of other investigated variants were identified between control women and those with RPL. No considerable link of F5 1691G > A/4070A > G, MTHFR 677C > T/1298A > C, and APOE 388 T > C/526C > T haplotypes with RPL risk was demonstrated. F13A1 G103T, FGB - 455G > A, and ITGB3 T1565C variants are connected to a higher likelihood of developing RPL and, hence, may have the potential to identify those women at risk of RPL, thereby, improving RPL susceptibility prediction. Incorporating molecular testing of thrombophilic and hypofibrinolytic genetic variants into routine workup could confer a promising approach for refined RPL risk assessment.
尽管已经确定了多种复发性妊娠丢失 (RPL) 的病因，但仍有 50-70%的 RPL 病例仍未得到明确解释，特发性 RPL 仍然是一个严重的医学挑战。大量研究已经探讨了 RPL 与凝血和/或纤维蛋白溶解因子编码基因变异之间的相关性。然而，这些变异与 RPL 之间的关联证据仍然存在分歧。我们旨在探讨血栓形成和低纤维蛋白溶解基因变异与 RPL 发生发展的关系。本研究纳入了 200 名沙特女性，包括 150 名经历 RPL 的女性和 50 名健康女性。共检测了 13 种基因变异，包括 FV G1691A、FV A4070G、F2 G20210A、F13A1 G103T、FGB-455G>A、PAI-1-675 4G/5G、ITGB3 T1565C、MTHFR C677T、MTHFR A1298C、ACE I/D、APOB G10708A、APOE T388C 和 APOE C526T。使用 ViennaLab StripAssay 对经历 RPL 的女性和对照组女性进行基因分型。与对照组女性相比，经历 RPL 的女性 F13A1 103T、FGB-455A 和 ITGB3 1565C 等位基因的频率显著更高（p<0.001）。在对照组女性和经历 RPL 的女性之间，其他检测到的变异的流行率没有差异。没有证据表明 F5 1691G>A/4070A>G、MTHFR 677C>T/1298A>C 和 APOE 388T>C/526C>T 单倍型与 RPL 风险有关。F13A1 G103T、FGB-455G>A 和 ITGB3 T1565C 变异与发生 RPL 的可能性更高相关，因此，这些变异可能有助于识别那些有发生 RPL 风险的女性，从而提高对 RPL 易感性的预测。将血栓形成和低纤维蛋白溶解遗传变异的分子检测纳入常规检测可能为精细评估 RPL 风险提供一种很有前途的方法。
