Causal associations between inflammatory cytokines and hypertensive disorders.

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.