Zhong Rongrong, Guo Yifen, Huang Jianxing, Yang Yingao, Ren Shuyue, Gu Yan, Lei Ping, Gao Zhixian
Deparment of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Department of Family Planning, The Second Hospital of Tianjin Medical University, Tianjin, China.
Front Genet. 2024 Aug 6;15:1372164. doi: 10.3389/fgene.2024.1372164. eCollection 2024.
Preeclampsia (PE) is a global pregnancy concern, characterized by hypertension with an unclear etiology. This study employs Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to clarify its genetic and molecular roots, offering insights into diagnosis and treatment avenues.
We integrated PE-specific genome-wide association study (GWAS) data, expression and protein quantitative trait loci (eQTL and pQTL) data, and single-cell data from peripheral blood mononuclear cells (PBMCs). We identified highly variable genes using single-cell information and employed MR to determine potential causality. We also combined pQTL and GWAS data, discerned genes positively associated with PE through scRNA-seq, and leveraged the Enrichr platform to unearth drug-gene interactions.
Our scRNA-seq pinpointed notable cell type distribution variances, especially in T helper cells (Th cells), between PE and control groups. We unveiled 591 highly variable genes and 6 directly PE-associated genes. Although MR revealed correlations with PE risk, pQTL analysis was inconclusive due to data constraints. Using DSigDB, 93 potential therapeutic agents, like Retinoic acid targeting core genes (IFITM3, NINJ1, COTL1, CD69, and YWHAZ), emerged as prospective multi-target treatments.
Utilizing MR and scRNA-seq, this study underscores significant cellular disparities, particularly in Th cells, and identifies crucial genes related to PE. Despite some limitations, these genes have been revealed in PE's underlying mechanism. Potential therapeutic agents, such as Retinoic acid, suggest promising treatment pathways.
子痫前期（PE）是一个全球关注的妊娠问题，其特征为高血压，病因不明。本研究采用孟德尔随机化（MR）和单细胞RNA测序（scRNA-seq）来阐明其遗传和分子根源，为诊断和治疗途径提供见解。
我们整合了特定于PE的全基因组关联研究（GWAS）数据、表达和蛋白质定量性状位点（eQTL和pQTL）数据以及外周血单核细胞（PBMC）的单细胞数据。我们利用单细胞信息鉴定高度可变基因，并采用MR确定潜在因果关系。我们还结合了pQTL和GWAS数据，通过scRNA-seq识别与PE呈正相关的基因，并利用Enrichr平台挖掘药物-基因相互作用。
我们的scRNA-seq确定了PE组和对照组之间显著的细胞类型分布差异，特别是在辅助性T细胞（Th细胞）中。我们发现了591个高度可变基因和6个与PE直接相关的基因。虽然MR揭示了与PE风险的相关性，但由于数据限制，pQTL分析尚无定论。使用DSigDB，93种潜在治疗药物，如靶向核心基因（IFITM3、NINJ1、COTL1、CD69和YWHAZ）的视黄酸，成为前瞻性多靶点治疗药物。
本研究利用MR和scRNA-seq强调了显著的细胞差异，特别是在Th细胞中，并鉴定了与PE相关的关键基因。尽管存在一些局限性，但这些基因已在PE的潜在机制中被揭示。视黄酸等潜在治疗药物提示了有前景的治疗途径。
