Key result
Key RAAS, NOS3, and circadian gene variants are linked to increased hypertension risk in Indian populations.
Why the study?
Despite genome-wide association studies identifying blood pressure loci worldwide, integration of these findings within the genetically varied Indian setting remains limited.
Do specific genetic polymorphisms increase the risk of hypertension in Indian populations?
Systematic Review
Do specific genetic polymorphisms increase the risk of hypertension in Indian populations?
Specific genetic variants in the RAAS, endothelial nitric oxide, and circadian pathways are significantly associated with hypertension risk in Indian populations, highlighting the need for ancestry-specific genomic studies.
Should not yet change hypertension care in Indian patients; extends SNP associations in renin–angiotensin–aldosterone, nitric oxide, and circadian pathways to this ancestry.
Background Hypertension continues to be a major public health issue in India, with increasing incidence associated with both lifestyle factors and genetic susceptibility. Despite genome-wide association studies identifying several loci related with blood pressure worldwide, there is a paucity of integration of these findings within the genetically varied Indian setting. Objective This systematic review aims to compile current information on single-nucleotide polymorphisms linked to hypertension in Indian communities and to elucidate their biological significance by bioinformatics analysis. Methods Using PubMed, Scopus, Embase, and Google Scholar, we conducted a systematic review of studies from 2000 to 2025 following PRISMA guidelines. Two reviewers individually screened and extracted data from studies related to SNPs associated to hypertension in Indians. Study quality was assessed using Q-Genie Tool. Functional and pathway studies have been conducted by SNPnexus, Enrichr, STRING, and GTEx. Result Twenty-two SNPs across 14 genes were evaluated in Indian cohorts, with several variants showing statistically significant associations with hypertension in at least one included study, particularly within the renin–angiotensin–aldosterone, endothelial nitric oxide, and circadian pathways. Functional annotation identified MTHFR rs1801133 as potentially affecting protein function, while several coding and noncoding variants showed predicted functional or regulatory activity. Pathway analysis highlighted hormonal regulation, vasodilation, and nitric oxide biosynthesis. eQTL analysis showed tissue-specific effects in arteries and vascular cells. Conclusion This is the first systematic study of Indian hypertension using genetic association data and functional bioinformatics. The findings emphasize the relevance of ancestry-specific genomes and the necessity for large-scale, multi-ethnic investigations to guide Indian hypertension precision therapy.
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Sivakumar et al. (2026) conducted a systematic review in Hypertension. Genetic polymorphisms (SNPs) vs. Normotensive controls was evaluated on Association of single-nucleotide polymorphisms with hypertension. Several single-nucleotide polymorphisms, particularly within the renin-angiotensin-aldosterone, endothelial nitric oxide, and circadian pathways, were significantly associated with hypertension in Indian populations.
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