A Systematic Review on Genetic Polymorphisms Associated with Hypertension Risk

Abstract

Background: Hypertension is a major global public health burden with a significant heritable component. Despite extensive genomic research, evidence linking specific genetic polymorphisms to hypertension risk remains inconsistent, partly due to a lack of diversity in study populations and methodological heterogeneity. Aim: This systematic review aimed to synthesise and critically appraise evidence of genetic polymorphisms associated with essential hypertension risk in adults, with a specific focus on population diversity and methodological quality. Methods: The review followed PRISMA guidelines. A comprehensive search of five databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library) was conducted. Observational studies (case-control, cohort) investigating specific polymorphisms in adults with essential hypertension were included. Two reviewers independently performed study selection, data extraction, and quality assessment using the Critical Appraisal Skills Programme (CASP) checklist. A narrative synthesis was conducted. Results: Five studies (total n = 3,851 participants) were included. Quality assessment using the CASP tool revealed that most case-control studies were of moderate quality (rated as "Fair"), limited by factors such as modest sample sizes and hospital-based recruitment. Findings indicated that genetic risk is highly population-specific. For example, the ACE I/D polymorphism was significantly associated with hypertension in a North Indian population but showed no association in a Senegalese cohort. A high-quality ("Good") longitudinal Japanese cohort study demonstrated that polygenic accumulation of four SNPs predicted 12-year hypertension risk (OR up to 16.9). Novel associations were reported for GPR158 in a Han Chinese population and *PAI-1* in North Indian participants. Conclusion: This review underscores the polygenic and population-specific architecture of hypertension. The current evidence base, marked by methodological limitations and ancestry-specific findings, is insufficient for the clinical application of individual polymorphism testing. Future research must prioritise large, diverse population-based cohorts, robust study designs, and investigations of gene-environment interactions to enable equitable progress in precision public health.