biostudies-literatureUnknown31Li X<h4>Background</h4>Several inflammatory cytokines (ICs) have been implicated in the development of hypertensive disorders. This study aimed to establish a causal relationship between 91 ICs and hypertensive disorders using Mendelian randomization (MR).<h4>Methods</h4>Single nucleotide polymorphisms associated with 91 ICs, hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were obtained from publicly available genome-wide association studies. MR analyses were conducted using inverse variance weighting as the primary method, complemented by MR-Egger and weighted median approaches. Significant ICs were further analyzed through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analyses.<h4>Results</h4>A total of 18 ICs exhibited significant associations with at least 1 hypertensive disorder, with 8, 7, 7, and 5 ICs associated with hypertension, SBP, DBP, and MAP, respectively. Among these, fibroblast growth factor 5 (FGF5) was uniquely associated with all 4 hypertensive conditions. Additionally, FGF5 was identified as a central hub in the PPI network. KEGG pathway analysis highlighted the involvement of the mitogen-activated protein kinase (MAPK) signaling pathway.<h4>Conclusions</h4>This study underscores the pivotal role of FGF5 and MAPK signaling pathway in the pathogenesis of hypertensive disorders. Targeting inflammatory pathways may offer therapeutic strategies for hypertension management.Clinical hypertensione27https://www.ebi.ac.uk/biostudies/studies/S-EPMC12411069biostudies-literatureCausal associations between inflammatory cytokines and hypertensive disorders.PMC12411069Qian HLi XYang YGong ZfalseCausal associations between inflammatory cytokines and hypertensive disorders.<h4>Background</h4>Several inflammatory cytokines (ICs) have been implicated in the development of hypertensive disorders. This study aimed to establish a causal relationship between 91 ICs and hypertensive disorders using Mendelian randomization (MR).<h4>Methods</h4>Single nucleotide polymorphisms associated with 91 ICs, hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were obtained from publicly available genome-wide association studies. MR analyses were conducted using inverse variance weighting as the primary method, complemented by MR-Egger and weighted median approaches. Significant ICs were further analyzed through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analyses.<h4>Results</h4>A total of 18 ICs exhibited significant associations with at least 1 hypertensive disorder, with 8, 7, 7, and 5 ICs associated with hypertension, SBP, DBP, and MAP, respectively. Among these, fibroblast growth factor 5 (FGF5) was uniquely associated with all 4 hypertensive conditions. Additionally, FGF5 was identified as a central hub in the PPI network. KEGG pathway analysis highlighted the involvement of the mitogen-activated protein kinase (MAPK) signaling pathway.<h4>Conclusions</h4>This study underscores the pivotal role of FGF5 and MAPK signaling pathway in the pathogenesis of hypertensive disorders. Targeting inflammatory pathways may offer therapeutic strategies for hypertension management.2025-01-01T00:00:00Z20252026-04-14T03:25:44.594Z2026-04-14T03:13:51.458ZS-EPMC124110694091822110.5646/ch.2025.31.e27