Functional Pathway
Analysis of Genetic Variants associated with Hypertension: A Comprehensive In Silico
Approach
Molakala Pavan Kumar Reddy, Goutham G., Kavya J. and Adiga Usha
Res. J. Biotech.; Vol. 20(10); 108-120;
doi: https://doi.org/10.25303/2010rjbt1080120; (2025)
Abstract
Hypertension is a complex multifactorial disorder with significant genetic components.
Genome-wide association studies (GWAS) have identified several genetic variants
associated with hypertension. This study aimed to identify biological pathways and
molecular mechanisms potentially involved in hypertension pathogenesis through in
silico functional analysis of GWAS-identified variants. We conducted a comprehensive
pathway analysis of five genes (CHRM3, ATP2B1, CACNB2, MSRA, UMOD and ZNF831) previously
associated with hypertension through GWAS. Multiple databases enriched biological
processes, cellular components, molecular functions, metabolic pathways, miRNA targets,
protein-protein interactions and gene expression signatures. Our analysis revealed
significant enrichment in several pathways critical to hypertension pathophysiology.
Key biological processes included regulation of smooth muscle contraction (p=2.65×10^-5),
vasoconstriction (p=4.53×10^-5) and calcium ion transport (p=5.65×10^-5). Molecular
function analysis highlighted calcium ion transmembrane transporter activity (p=3.15×10^-4).
Enriched cellular components included basolateral plasma membrane (p=1.97×10^-3)
and voltage-gated calcium channel complexes (p=1.94×10^-2). Pathway analysis identified
significant associations with sensory processing of sound (p=3.24×10^-4), cardiac
conduction (p=1.14×10^-3) and regulation of insulin secretion (p=4.14×10^-4).
Our findings provide new insights into the molecular mechanisms underlying hypertension,
particularly highlighting the importance of calcium signaling, smooth muscle contraction
and vasoconstriction. These results suggest potential therapeutic targets and may
contribute to the development of personalized medicine approaches for hypertension
management.
