Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi 13488, Republic of Korea.
Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam, Gyeonggi 13496, Republic of Korea.
Mol Med Rep. 2018 Aug;18(2):2417-2426. doi: 10.3892/mmr.2018.9202. Epub 2018 Jun 21.
Recurrent pregnancy loss (RPL) is defined as ≥2 consecutive pregnancy losses, and can be caused by various factors, including genetics, chromosomal abnormalities, thrombophilia, immune disorders, nutritional factors, environmental factors, psychological stress or maternal infections; however, as many as 50% of RPL cases are idiopathic. In the present study, the role of genetic polymorphisms in RPL was investigated. Four gene polymorphisms were selected by whole exome sequencing, including membrane spanning 4‑domains A14 (MS4A14)D>I (rs3217518), solute carrier family 2 member 7 (SLC2A7)D>I (rs60746313), pregnancy specific β‑1‑glycoprotein 9 (PSG9)C>T (rs3746297) and ATP binding cassette subfamily B member 5 (ABCB5)C>G (rs17143187), and the aim was to investigate their association with RPL in Korean women. Genotyping was performed using polymerase chain reaction‑restriction fragment length polymorphism assay. Allele combination analysis revealed that the four‑allele combination I‑D‑T‑G, (MS4A14/SLC2A7/PSG9/ABCB5) was associated with a decreased risk for RPL. Interaction analysis demonstrated that the following genotypes: MS4A14 DI+II, SLC2A DI+II and ABCB 5 CG+GG, were associated with a prothrombin time ≥12 sec and with RPL risk. It may be concluded that the four gene polymorphisms do not affect RPL individually, but are associated with RPL when in combination with other genes or blood coagulation factors. Notably, the MS4A14 I allele, with a prothrombin time ≥12 sec, may be a potential biomarker for diagnosis, prevention and prognosis of RPL.
复发性流产（RPL）定义为≥2 次连续妊娠丢失，其病因可能包括遗传因素、染色体异常、血栓形成倾向、免疫紊乱、营养因素、环境因素、心理压力或母体感染等，但多达 50%的 RPL 病例为特发性。本研究旨在探讨 RPL 中遗传多态性的作用。通过全外显子组测序选择了 4 个基因多态性，包括跨膜 4 结构域 A14（MS4A14）D>I（rs3217518）、溶质载体家族 2 成员 7（SLC2A7）D>I（rs60746313）、妊娠特异性β-1-糖蛋白 9（PSG9）C>T（rs3746297）和 ATP 结合盒亚家族 B 成员 5（ABCB5）C>G（rs17143187），旨在探讨它们与韩国女性 RPL 的关系。采用聚合酶链反应-限制性片段长度多态性分析进行基因分型。等位基因组合分析显示，I-D-T-G 四等位基因组合（MS4A14/SLC2A7/PSG9/ABCB5）与 RPL 风险降低相关。交互分析表明，MS4A14 DI+II、SLC2A DI+II 和 ABCB5 CG+GG 基因型与凝血酶原时间≥12 秒及 RPL 风险相关。综上可知，这 4 个基因多态性单独不影响 RPL，但与其他基因或凝血因子联合时与 RPL 相关。值得注意的是，MS4A14 I 等位基因与凝血酶原时间≥12 秒可能是 RPL 诊断、预防和预后的潜在生物标志物。
