Association Between ACE (I/D) Polymorphism and Essential Hypertension (EH): An Updated Systematic Review and Meta-Analysis

TL;DR

This study finds a genetic link between the ACE D allele and essential hypertension in certain populations, which could help tailor public health strategies.

Contribution

The study provides updated evidence on the association between ACE (I/D) polymorphism and essential hypertension across diverse populations.

Findings

The ACE D allele is significantly associated with increased risk of essential hypertension in Indian, European, and Chinese populations.

Subgroup analyses show no significant association in African, Middle Eastern, and Hispanic populations.

Meta-analysis reveals consistent risk elevation across multiple genetic models (allelic, recessive, dominant, homozygote).

Abstract

Public health relevance—How does this work relate to a public health issue?
Essential hypertension (EH) is a major global contributor to morbidity and mortality and is a leading risk factor for cardiovascular diseases (CVDs) such as stroke, heart disease, and heart failure.Understanding population-specific genetic risk factors is directly relevant to public health because hypertension prevalence varies across ethnic groups, and early detection and prevention strategies depend on accurate risk stratification.

Essential hypertension (EH) is a major global contributor to morbidity and mortality and is a leading risk factor for cardiovascular diseases (CVDs) such as stroke, heart disease, and heart failure.

Understanding population-specific genetic risk factors is directly relevant to public health because hypertension prevalence varies across ethnic groups, and early detection and prevention strategies depend on accurate risk stratification.

Public health significance—Why is this work of significance to public health?
The meta-analysis identifies a significant association between the ACE D allele and increased risk of EH in several populations (Indian, European, Chinese), highlighting the genetic component in hypertension and its interplay with environmental drivers.Since EH is highly prevalent and modifiable, understanding contributing genetic factors can enhance targeted intervention strategies, potentially reducing the burden of CVDs globally.

The meta-analysis identifies a significant association between the ACE D allele and increased risk of EH in several populations (Indian, European, Chinese), highlighting the genetic component in hypertension and its interplay with environmental drivers.

Since EH is highly prevalent and modifiable, understanding contributing genetic factors can enhance targeted intervention strategies, potentially reducing the burden of CVDs globally.

Public health implications—What are the key implications or messages for practitioners, policy makers and/or researchers in public health?
For practitioners and researchers: Knowledge of genetic risk may guide personalised risk assessment and preventive counselling, particularly in populations in which stronger associations are observed.For policymakers: Findings underscore the need for ethnically tailored public health strategies, including hypertension screening guidelines, culturally and genetically informed prevention programs, and investment in genomic public health infrastructure.

For practitioners and researchers: Knowledge of genetic risk may guide personalised risk assessment and preventive counselling, particularly in populations in which stronger associations are observed.

For policymakers: Findings underscore the need for ethnically tailored public health strategies, including hypertension screening guidelines, culturally and genetically informed prevention programs, and investment in genomic public health infrastructure.

Background: Essential hypertension (EH) refers to elevated arterial blood pressure with unknown etiology, which becomes more prevalent with age. Although the D allele of the ACE (I/D) polymorphism has been linked to EH, this association is not consistent across global populations. This systematic review and meta-analysis examined the relationship between the ACE (I/D) polymorphism and EH in diverse populations to determine the comparability of effect sizes and explore potential implications for public health planning. Methods: Case–control and cohort studies published in the last 20 years were reviewed from the main databases (PubMed, Scopus and Embase) using specific inclusion and exclusion criteria. Genotype data were used in meta-analyses using different genetic models. Results: Twenty-two studies with 7690 participants (3886 cases and 3804 controls) were included. Significant associations were observed between the ACE D allele and EH across allelic (OR = 1.37, 95% CI: 1.14–1.63), recessive (OR = 1.61, 95% CI: 1.21–2.13), dominant (OR = 1.37, 95% CI: 1.13–1.67), and homozygote (OR = 1.79, 95% CI: 1.31–2.45) models. Subgroup analyses showed significant associations in Indian and European populations, while African, Middle Eastern and Hispanic groups showed no statistically significant associations. Conclusions: The findings support a significant association between the ACE D allele and EH in several populations, though associations vary by ethnicity.

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