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Background Preeclampsia is a pregnancy-related condition that causes high blood pressure and proteinuria after 20 weeks of pregnancy. It is linked to increased maternal mortality, organ malfunction, and foetal development limitation. In this view, there is a need critical to identify biomarkers for the early detection of preeclampsia. The objective of this study is to discover critical genes and explore medications for preeclampsia treatment that may influence these genes. Methods Four datasets, including GSE10588, GSE25906, GSE48424 and GSE60438 were retrieved from the Gene Expression Omnibus database. The GSE10588, GSE25906, and GSE48424 datasets were then removed the batch effect using the “sva” R package and merged into a complete dataset. The differentially expressed genes (DEGs) were identified using the “limma” R package. The potential small-molecule agents for the treatment of PE was further screened using the Connective Map (CMAP) drug database based on the DEGs. Further, Weight gene Co-expression network (WGNCA) analysis was performed to identified gene module associated with preeclampsia, hub genes were then identified using the logistic regression analysis. Finally, the immune cell infiltration level of genes was evaluated through the single sample gene set enrichment analysis (ssGSEA). Results A total of 681 DEGs (376 down-regulated and 305 up-regulated genes) were identified between normal and preeclampsia samples. Then, Dexamethasone, Prednisone, Rimexolone, Piretanide, Trazodone, Buflomedil, Scoulerin, Irinotecan, and Camptothecin drugs were screened based on these DEGs through the CMAP database. Two modules including yellow and brown modules were the most associated with disease through the WGCNA analysis. KEGG analysis revealed that the chemokine signaling pathway, Th1 and Th2 cell differentiation, B cell receptor signalling pathway and oxytocin signalling pathway were significantly enriched in these modules. Moreover, two key genes, PLEK and LEP were evaluated using the univariate and multivariate logistic regression analysis from the hub modules. These two genes were further validated in the external validation cohort GSE60438 and qRT-PCR experiment. Finally, we evaluated the relationship between immune cell and two genes. Conclusion In conclusion, the present study investigated key genes associated with PE pathogenesis that may contribute to identifying potential biomarkers, therapeutic agents and developing personalized treatment for PE.

Osteoporosis is a chronic multifactorial disease characterized by deterioration of bone mass and is vulnerable to bone fracture. Plasminogen activator inhibitor-1 (PAI-1) is an important molecule for maintenance of optimum bone mass. Several single-nucleotide polymorphisms (SNPs) in PAI-1 have been reported to alter PAI-1 expression and/ or the translational level. In this report, we explored the possible role of common PAI-1 gene polymorphisms on predisposition to osteoporosis in a Chinese cohort. A total of 364 post-menopausal Chinese women diagnosed of having osteoporosis and 350 healthy females hailing from similar areas were enrolled in this study. Five common SNPs (−844G > A, −6754G/5G, +43G > A, +9785G > A and +11053T > G) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Relative expression of PAI-1 mRNA and plasma PAI-1 levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Prevalence of homozygous mutant (5G/5G) and minor allele (5G) of PAI-1 (−675 4G/5G) polymorphism was significantly more frequent in patients than in healthy controls (5G/5G: P < 0.0001, odds ratio (OR) = 3.18; 5G: P < 0.0001, OR = 1.65). Both plasma PAI-1 and relative mRNA expression levels were significantly lower in patients compared to healthy controls. Interestingly, the quantity of plasma PAI-1 and mRNA expression was correlated with PAI-1 (−675 4G/5G) polymorphism: subjects with 4G/4G genotype had elevated PAI-1 in comparison to homozygous mutant, and displayed lower quantity of PAI-1 protein and mRNA values. PAI-1 (−675 4G/5G) mutant is associated with susceptibility to development of osteoporosis in post-menopausal Chinese women. Furthermore, this variant in the promoter region alters plasma protein levels and relative expression of PAI-1.