Department of Obstetrics and Gynecology, College of Medicine, Ewha Medical Research Institute, Ewha Womans University Mokdong Hospital, Seoul, Korea.
Division of Biobank, Korea National Institute of Health (KNIH), Korea Disease Control and Prevention Agency (KDCA), Cheongju, Korea.
PLoS One. 2023 Nov 29;18(11):e0294948. doi: 10.1371/journal.pone.0294948. eCollection 2023.
Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, it is crucial to predict and prevent PTB. Advancements enable the prediction and prevention of PTB using genetic approaches, especially by investigating its correlation with single nucleotide polymorphisms (SNPs). We aimed to identify impactive and relevant SNPs for the prediction of PTB via whole-genome sequencing analyses of the blood of 31 pregnant women with PTB (n = 13) and term birth (n = 18) who visited the Ewha Womans University Mokdong Hospital from November 1, 2018 to February 29, 2020. A genome-wide association study was performed using PLINK 1.9 software and 256 SNPs were selected and traced through protein-protein interactions. Moreover, a validation study by genotyping was performed on 60 other participants (preterm birth, n = 30; term birth, n = 30) for 25 SNPs related to ion channel binding and receptor complex pathways. Odds ratios were calculated using additive, dominant, and recessive genetic models. The risk of PTB in women with the AG allele of rs2485579 (gene name: RYR2) was significantly 4.82-fold increase, and the risk of PTB in women with the AG allele of rs7903957 (gene name: TBX5) was significantly 0.25-fold reduce. Our results suggest that rs2485579 (in RYR2) can be a genetic marker of PTB, which is considered through the association with abnormal cytoplasmic Ca2+ concentration and dysfunctional uterine contraction due to differences of RYR2 in the sarcoplasmic reticulum.
早产（PTB）是指妊娠 37 周前分娩。早产儿的新生儿发病率和死亡率均高于足月儿；因此，预测和预防 PTB 至关重要。随着技术的进步，可以通过遗传方法来预测和预防 PTB，尤其是通过研究其与单核苷酸多态性（SNP）的相关性。我们旨在通过对 31 名患有 PTB（n=13）和足月分娩（n=18）的孕妇的血液进行全基因组测序分析，来识别对 PTB 有影响和相关的 SNP，这些孕妇于 2018 年 11 月 1 日至 2020 年 2 月 29 日期间就诊于梨花女子大学木洞医院。使用 PLINK 1.9 软件进行全基因组关联研究，选择并追踪了 256 个 SNP 进行蛋白质-蛋白质相互作用分析。此外，对另外 60 名参与者（早产，n=30；足月分娩，n=30）进行了与离子通道结合和受体复合物途径相关的 25 个 SNP 的基因分型验证研究。使用加性、显性和隐性遗传模型计算比值比。rs2485579（基因名称：RYR2）AG 等位基因携带者发生 PTB 的风险显著增加 4.82 倍，rs7903957（基因名称：TBX5）AG 等位基因携带者发生 PTB 的风险显著降低 0.25 倍。我们的研究结果表明，rs2485579（位于 RYR2 中）可以作为 PTB 的遗传标志物，这是由于肌浆网中 RYR2 的差异导致细胞质 Ca2+浓度异常和子宫收缩功能障碍。
