Ryu Chang Soo, Sakong Jung Hyun, Ahn Eun Hee, Kim Jung Oh, Ko Daeun, Kim Ji Hyang, Lee Woo Sik, Kim Nam Keun
Department of Biomedical Science, College of Life Science, CHA University, Seongnam, 13488, South Korea.
Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Seongnam, 13496, South Korea.
Genes Genomics. 2019 Jan;41(1):61-70. doi: 10.1007/s13258-018-0738-5. Epub 2018 Sep 10.
This study was purposed to investigate whether genetic polymorphisms in the function of stop-gain are associated with a fetal or placental development play roles and a development of idiopathic recurrent pregnancy loss (RPL) in Korean females. Three stop-gain polymorphisms were selected using next-generation sequencing screening, which allows for the rigorous examination and discovery of previously uncharacterized stop-gain genes and stop-gain expression profiles. Accordingly, we investigated the association of stop-gain polymorphisms in Korean women with RPL. Three functional polymorphisms in the TAS2R46G>A (rs2708381), OR4C16G>A (rs1459101), and OR4X1A>T (rs10838851) genes were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism assays and real-time PCR analysis. We determined that the OR4C16G>A polymorphism was associated with idiopathic RPL in Korean women (Adjusted odds ratio [AOR] 1.782; 95% confidence interval [CI] 1.004-3.163; P = 0.048, and AOR 1.766; 95% CI 1.020-3.059; P = 0.042). In addition, the prevalence of RPL was increased in women with the OR4C16GA + AA genotype and blood coagulation measures of prothrombin time (PT) > 10.4 s (AOR 8.292; 95% CI 2.744-25.054). We suggest that the OR4C16G>A polymorphism might serve as a clinically useful biomarker for the development, prevention, and prognosis of RPL.
本研究旨在调查韩国女性中终止密码子获得功能的基因多态性是否与胎儿或胎盘发育相关，以及是否在不明原因复发性流产（RPL）的发生发展中起作用。通过下一代测序筛选选择了三个终止密码子获得多态性，该技术能够严格检测和发现先前未被表征的终止密码子获得基因及终止密码子获得表达谱。据此，我们研究了韩国女性中终止密码子获得多态性与RPL的相关性。采用聚合酶链反应（PCR）-限制性片段长度多态性分析和实时PCR分析对TAS2R46G>A（rs2708381）、OR4C16G>A（rs1459101）和OR4X1A>T（rs10838851）基因中的三个功能多态性进行基因分型。我们确定，OR4C16G>A多态性与韩国女性的不明原因RPL相关（校正比值比[AOR]1.782；95%置信区间[CI]1.004 - 3.163；P = 0.048，以及AOR 1.766；95% CI 1.020 - 3.059；P = 0.042）。此外，携带OR4C16GA + AA基因型且凝血指标凝血酶原时间（PT）>10.4秒的女性中RPL的患病率增加（AOR 8.292；95% CI 2.744 - 25.054）。我们认为，OR4C16G>A多态性可能作为RPL发生、预防和预后的一种临床有用生物标志物。
