Jang Eun Jeong, Lee Da Hoon, Song Yubin, Kim Jung Sun, Kim Young Ju, Yee Jeong, Gwak Hye Sun
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea.
Department of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea.
J Pers Med. 2025 May 21;15(5):212. doi: 10.3390/jpm15050212.
Ritodrine, a tocolytic agent used to delay preterm labor, can cause several cardiovascular-associated adverse events (AEs). This study aimed to examine the relationship between gene polymorphisms in peroxisome proliferator-activated receptor gamma () and PPARG coactivator-1α () and the occurrence of ritodrine-induced AEs. Additionally, a risk-scoring system was developed to identify patients at high risk of AEs. Patients aged 18 years or older who were administered ritodrine to manage preterm labor with intact membranes and uterine contractions occurring at 20-36 weeks of gestation were enrolled in this study. A total of 70 common and variants (minor allele frequency ≥ 0.2) with low linkage disequilibrium (r < 0.8) were selected from an Axiom™ Precision Medicine Research Array (AMPRA). A total of 149 patients were included in the analysis. After adjusting for confounders (age, gestational age, and the maximum infusion rate), weight and rs2946385, rs35523565, and rs2240748 of were identified as significant predictors associated with ritodrine-induced AEs. Based on the risk-scoring system, the predicted probabilities of AEs for patients with scores of 0, 1, 2, 3, 4, and 5 points were 4%, 9%, 18%, 35%, 55%, and 74%, respectively. The AUROC for the risk score predicting ritodrine-induced AEs was 0.729 (95% CI: 0.672-0.831, < 0.001). This study indicates that ritodrine-induced AEs are related to polymorphisms. A risk-scoring system based on genetic variants showed moderate predictive ability for ritodrine-induced AEs, suggesting potential utility in females with preterm labor.
利托君是一种用于延迟早产的宫缩抑制剂，可引发多种与心血管相关的不良事件（AE）。本研究旨在探讨过氧化物酶体增殖物激活受体γ（PPARG）和PPARG辅激活因子-1α（PPARGC1A）的基因多态性与利托君所致不良事件发生之间的关系。此外，还开发了一种风险评分系统以识别发生不良事件的高危患者。本研究纳入了年龄在18岁及以上、接受利托君治疗以处理胎膜完整且妊娠20 - 36周出现子宫收缩的早产患者。从Axiom™精准医学研究阵列（AMPRA）中选取了70个具有低连锁不平衡（r < 0.8）的常见PPARGC1A和PPARG变体（次要等位基因频率≥0.2）。共有149例患者纳入分析。在对混杂因素（年龄、孕周和最大输注速率）进行校正后，体重以及PPARGC1A的rs2946385、rs35523565和rs2240748被确定为与利托君所致不良事件相关的显著预测因素。基于该风险评分系统，评分为0、1、2、3、4和5分的患者发生不良事件的预测概率分别为4%、9%、18%、35%、55%和74%。预测利托君所致不良事件的风险评分的受试者工作特征曲线下面积（AUROC）为0.729（95%置信区间：0.672 - 0.831，P < 0.001）。本研究表明，利托君所致不良事件与PPARGC1A多态性有关。基于基因变体的风险评分系统对利托君所致不良事件显示出中等预测能力，提示在早产女性中具有潜在应用价值。
