Dang Chunxiao, Duan Yanan, Liu Pengfei, Liu Jinxing, Yu Xiao, Wang Jiangping
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, 257000, China.
Reprod Sci. 2025 Apr;32(4):1147-1154. doi: 10.1007/s43032-025-01809-7. Epub 2025 Feb 28.
Lipidomes are thought to be associated with preeclampsia (PE). In addition, the immune response has been reported to play an important role in the development of PE. However, the causal relationship between the three remains unclear. We aimed to determine whether genetically predicted lipidomes, immunophenotypes, have a causal effect on PE, and also to explore whether immunophenotypes mediate the causal effect of lipidomes on PE. Two-step Mendelian randomization (MR) analysis, mainly using the inverse variance weighted (IVW) method, was performed to estimate the correlation between lipidomes, immunophenotypes, and PE and the potential effect of mediators. Bayesian analysis was also performed to improve the accuracy of the results. Finally, heterogeneity and horizontal polytropy tests were performed. The STROBE-MR checklist for the reporting of MR studies was used in this study. A total of 9 lipidomes and 25 immunophenotypes were found to be causally associated with the risk of PE, and mediation MR analyses identified HLA DR + Natural Killer %Natural Killer, HLA DR on B cell, and CD28 + CD45RA + CD8 T cell Absolute Count as mediators of the causal association between lipidomes and PE. Our MR study genetically suggests that lipidomes and immunophenotypes play an important role in the pathogenesis of PE, highlighting the potential mediating role of the three immunophenotypes, which contributes to a more in-depth understanding of the pathomechanisms of PE, thus providing new insights for the development of preventive and therapeutic strategies.
脂质组被认为与子痫前期（PE）有关。此外，据报道免疫反应在PE的发展中起重要作用。然而，三者之间的因果关系仍不清楚。我们旨在确定基因预测的脂质组、免疫表型是否对PE有因果影响，并探讨免疫表型是否介导脂质组对PE的因果作用。采用两步孟德尔随机化（MR）分析，主要使用逆方差加权（IVW）方法，来估计脂质组、免疫表型和PE之间的相关性以及中介因素的潜在作用。还进行了贝叶斯分析以提高结果的准确性。最后，进行了异质性和水平多效性检验。本研究使用了MR研究报告的STROBE-MR清单。共发现9种脂质组和25种免疫表型与PE风险存在因果关联，中介MR分析确定HLA DR+自然杀伤细胞%自然杀伤细胞、B细胞上的HLA DR以及CD28+CD45RA+CD8 T细胞绝对计数为脂质组与PE之间因果关联的中介因素。我们的MR研究从基因角度表明脂质组和免疫表型在PE发病机制中起重要作用，突出了这三种免疫表型的潜在中介作用，有助于更深入地了解PE的发病机制，从而为预防和治疗策略的制定提供新的见解。
