Causal associations between inflammatory cytokines and hypertensive disorders
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Background: 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). Methods: 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. Results: 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. Conclusions: 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.
Abstract
Background: 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). Methods: 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. Results: 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. Conclusions: 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.