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Background <p>Hypertension is a multifaceted disorder with both genetic and environmental contributions. Key Single nucleotide polymorphisms (SNPs) have been linked to critical pathways controlling blood pressure, vascular tone, renal sodium reabsorption, and oxidative stress. This umbrella review summarizes evidence on 21 focal SNPs from ACE, ACE2, AGT, ADD1, ADRB1, ANP, ApoE, CYP11B2, CYP4F2, ENOS, GNB3, LIPC, LEPR, MTHFR, RNLS, STK39, TNF-α, and VDR determining the weight of association, credibility, and clinical significance.</p> Methods <p>This study included&#xa0;21 meta-analyses, a cumulative total of 392,314 participants were represented. SNPs were organized into six biological pathways: Renin–Angiotensin–Aldosterone System (RAAS), vascular tone, metabolism, oxidative stress, methylation, inflammation. Credibility evaluations included GRADE, Venice Criteria, AMSTAR-2, and NOS with Composite Score which ranked SNP’s based on association and reliability strength. The best predictive SNPs were determined using a Random Forest model.</p> Results <p>Polymorphisms in&#xa0;ACE (I/D), ApoE (ε4), TNF-α (G308A), eNOS (rs1799983), and MTHFR (C677T) showed strong associations (OR &gt; 2.0). Moderate associations included AGT (M235T), LEPR (Gln223Arg), STK39 (rs3754777), and CYP11B2 (C344T). The Random Forest model identified the top predictive SNPs as TNF-α (G308A), ApoE (ε4), and ACE (I/D).</p> Conclusion <p>In this umbrella&#xa0;review, the major genetic factors impacting hypertension is outlined with the help of meta-analysis, credibility analysis, and machine learning. SNPs with higher Composite Scores demonstrated stronger potential for clinical application and translational value, which enhances personalized medicine and individual healthcare. More work is required to more effectively prevent and treat hypertension by studying gene-environment interactions.</p>

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Comprehensive umbrella review of meta-analysis on genetic polymorphisms (SNPs) and their links to hypertension

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月1日

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  • Ahmed Naseer Kaftan

摘要

Background

Hypertension is a multifaceted disorder with both genetic and environmental contributions. Key Single nucleotide polymorphisms (SNPs) have been linked to critical pathways controlling blood pressure, vascular tone, renal sodium reabsorption, and oxidative stress. This umbrella review summarizes evidence on 21 focal SNPs from ACE, ACE2, AGT, ADD1, ADRB1, ANP, ApoE, CYP11B2, CYP4F2, ENOS, GNB3, LIPC, LEPR, MTHFR, RNLS, STK39, TNF-α, and VDR determining the weight of association, credibility, and clinical significance.

Methods

This study included 21 meta-analyses, a cumulative total of 392,314 participants were represented. SNPs were organized into six biological pathways: Renin–Angiotensin–Aldosterone System (RAAS), vascular tone, metabolism, oxidative stress, methylation, inflammation. Credibility evaluations included GRADE, Venice Criteria, AMSTAR-2, and NOS with Composite Score which ranked SNP’s based on association and reliability strength. The best predictive SNPs were determined using a Random Forest model.

Results

Polymorphisms in ACE (I/D), ApoE (ε4), TNF-α (G308A), eNOS (rs1799983), and MTHFR (C677T) showed strong associations (OR > 2.0). Moderate associations included AGT (M235T), LEPR (Gln223Arg), STK39 (rs3754777), and CYP11B2 (C344T). The Random Forest model identified the top predictive SNPs as TNF-α (G308A), ApoE (ε4), and ACE (I/D).

Conclusion

In this umbrella review, the major genetic factors impacting hypertension is outlined with the help of meta-analysis, credibility analysis, and machine learning. SNPs with higher Composite Scores demonstrated stronger potential for clinical application and translational value, which enhances personalized medicine and individual healthcare. More work is required to more effectively prevent and treat hypertension by studying gene-environment interactions.