Ko Eun Ju, Ahn Eun Hee, Park Hyeon Woo, Lee Jae Hyun, Kim Da Hwan, Kim Young Ran, Kim Ji Hyang, Kim Nam Keun
Division of Life Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea.
Department of Life Science, Graduate School, CHA University, Seongnoam 13488, Republic of Korea.
Int J Mol Sci. 2025 Aug 3;26(15):7505. doi: 10.3390/ijms26157505.
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 () rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain () rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha () rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 () rs2812 C > T; and platelet endothelial aggregation receptor 1 () rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262-4.969, = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551-6.830, = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403-9.307, = 0.008). The rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460-0.987, = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310-0.997, = 0.049). These findings indicate significant associations of the rs3809865 A > T and rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women.
复发性流产（RPL）的定义为妊娠20周前发生两次或更多次流产。RPL是育龄期女性的常见病症，全球每年报告约2300万例。高达5%的孕妇可能经历两次或更多次连续流产。既往研究调查了RPL的危险因素，包括产妇年龄、子宫病变、基因异常、感染因子、内分泌紊乱、血栓形成倾向和免疫功能障碍。然而，RPL是一种由遗传因素、环境因素（如饮食、生活方式和压力）、表观遗传因素和免疫系统复杂相互作用引起的疾病。此外，由于缺乏与RPL相关的遗传学研究，高达50%的病例病因仍不清楚。血小板在维持妊娠中起关键作用。本研究检测了血小板受体和配体基因变异，包括整合素β3亚基（）rs2317676 A>G、rs3809865 A>T；纤维蛋白原γ链（）rs1049636 T>C、rs2066865 T>C；糖蛋白1bα亚基（）rs2243093 T>C、rs6065 C>T；血小板内皮细胞黏附分子1（）rs2812 C>T；以及血小板内皮聚集受体1（）rs822442 C>A、rs12137505 G>A，与RPL患病率的关联。总共纳入了389例RPL患者和375例健康对照（均为韩国女性）。使用聚合酶链反应-限制性片段长度多态性和TaqMan基因分型检测对每个单核苷酸多态性进行基因分型。所有样本均在盆唐CHA医疗中心机构审查委员会批准下采集。rs3809865 A>T基因型与RPL患病率密切相关（流产[PL]≥2次：调整优势比[AOR]=2.505，9
