Xiang Yi, Lv Yanming, Fu Wenhao, Wen Jie, Li Baixiang, Li Xueting
Department of Hygienic Toxicology, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin 150081, China.
Int J Mol Sci. 2025 Jun 25;26(13):6103. doi: 10.3390/ijms26136103.
Several studies suggest a relationship between phthalates (PAEs) and allergic diseases in children. Therefore, we speculated that PAE exposure may be an important environmental factor causing allergic diseases. The present study employed meta-analysis and network toxicology to analyze the interactions and assess potential pathogenic pathways between prenatal and postnatal PAE exposure and childhood allergic diseases. This study found that prenatal PAEs exposure was positively associated with childhood wheezing and eczema (OR = 1.03, 1.05), and postnatal PAEs exposure was positively associated with childhood wheezing, eczema, and rhinitis (OR = 1.10, 1.05, 1.06). PAE exposure from dust may elicit distinct effects compared to direct exposure to PAEs. Furthermore, a large number of overlapping genes between disease targets and PAEs were identified. Enrichment analysis highlighted the association of PAE-targeted genes with biological pathways integral to allergic diseases. Molecular docking results indicated a strong link between the PAEs and the core proteins, such as SRC, AKT1, and HSP90AA1. These proteins are critically involved in the regulation of immune-inflammatory processes underlying allergic diseases. This discovery not only enhances our understanding of the relationship between environmental pollutants and child health but also provides a robust reference for experimental studies on the induction of childhood diseases by early-life exposure to environmental pollutants.
多项研究表明邻苯二甲酸酯(PAEs)与儿童过敏性疾病之间存在关联。因此,我们推测PAE暴露可能是导致过敏性疾病的一个重要环境因素。本研究采用荟萃分析和网络毒理学方法,分析产前和产后PAE暴露与儿童过敏性疾病之间的相互作用,并评估潜在的致病途径。本研究发现,产前PAE暴露与儿童喘息和湿疹呈正相关(OR = 1.03,1.05),产后PAE暴露与儿童喘息、湿疹和鼻炎呈正相关(OR = 1.10,1.05,1.06)。与直接接触PAEs相比,灰尘中的PAE暴露可能会产生不同的影响。此外,还鉴定出疾病靶点与PAEs之间存在大量重叠基因。富集分析突出了PAE靶向基因与过敏性疾病不可或缺的生物学途径之间的关联。分子对接结果表明PAEs与核心蛋白(如SRC、AKT1和HSP90AA1)之间存在紧密联系。这些蛋白在过敏性疾病潜在的免疫炎症过程调节中起关键作用。这一发现不仅增进了我们对环境污染物与儿童健康之间关系的理解,也为早期接触环境污染物诱发儿童疾病的实验研究提供了有力参考。