Exploring the shared molecular mechanisms of primary hypertension and IgA vasculitis through a case report and combining bioinformatics analysis

Qijiao Wei^1*Jiayan Feng¹Yifei Mu^2,3Qian Shen¹Li Sun¹Hong Xu¹Haimei Liu^1*

• ¹Children's Hospital, Fudan University, Shanghai, Shanghai Municipality, China
• ²First People’s Hospital of Zunyi, Zunyi, Guizhou Province, China
• ³The Third Affiliated Hospital of Zunyi Medical University, zunyi, China

BackgroundPrimary hypertension (PHTN) and IgA vasculitis (IgAV) are two prevalent medical conditions that affect the kidneys. This study aims to report this unusual case and investigate the biological mechanisms associated with the differentially expressed genes (DEGs) related to PHTN and IgAV through the application of bioinformatics tools.MethodsWe present the case of a boy diagnosed with PHTN and IgAV. Additionally, we explore the molecular mechanisms underlying both conditions. DEGs were analyzed, and gene functional enrichment was performed using the DAVID database. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized with Cytoscape software. The hub genes were identified using the MCODE plugin. Furthermore, the Connectivity Map L1000 platform was utilized to identify potential therapeutic agents.ResultsThe boy initially presented with malignant hypertension (MHT), and renal biopsy pathology indicated HN. Following regular use of antihypertensive medications, there was a significant improvement in blood pressure (BP), renal function, and the left ventricular hypertrophy index. However, he developed IgAV six years after the diagnosis of PHTN. A subsequent renal biopsy revealed IgAV nephritis, and the pathology associated with HN showed marked improvement. A total of 25 genes overlapping between the two sets. KEGG pathway analysis revealed that the DEGs were primarily associated with extracellular matrix (ECM) receptor interaction. Gene Ontology (GO) biological process analysis indicated that the 25 overlapping DEGs were significantly related to processes such as proteolysis, amyloid fibril formation, cAMP-mediated signaling, synaptic vesicle endocytosis, and receptor internalization. The significantly enriched terms related to changes in the cellular component of DEGs included platelet alpha granule membrane, nucleoplasm, and endocytic vesicle membrane. Changes in molecular function were primarily associated with protein binding. Using the Connectivity Map (CMap) database, the top 10 potential therapeutic agents were identified.ConclusionAggressive BP-lowering agents were necessary for managing PHTN. This study also reveals the common pathogenesis underlying both PHTN and IgAV. Moving forward, these shared hub genes could serve as novel targets for more in-depth mechanistic investigations and the development of new therapeutic interventions for individuals affected by PHTN and IgAV.