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Review
. 2025 May 1:2025:5530265.
doi: 10.1155/ijhy/5530265. eCollection 2025.

Impact of Renin-Angiotensin-Aldosterone System (RAAS) Gene Polymorphism in Essential Hypertension and Antihypertensive Drug Therapy: A Review

Archana Adhikari  1 , Chandrakala Sharma  1 , Mingma Lhamu Sherpa  2 , Gauthaman Karaunakran  3 , Mona Dhakal  4 , Anita Sharma  5
Affiliations
Review

Impact of Renin-Angiotensin-Aldosterone System (RAAS) Gene Polymorphism in Essential Hypertension and Antihypertensive Drug Therapy: A Review

Archana Adhikari et al. Int J Hypertens. .

Abstract

Genetic, demographic and environmental factors all play a role in the frequency of an intricate multifactorial condition known as hypertension. Approximately 30% and 50% of BP fluctuation are influenced by genetic variability. Many genetic studies have confirmed the link between genetic variability and susceptibility to essential hypertension; hence, identifying genes associated with essential hypertension susceptibility will aid in understanding the pathophysiology and their influence on how an individual responds towards the antihypertensive therapy. There are also controversial results highlighted in some reports. This review summarises genetic variants of the renin-angiotensin-aldosterone system (RAAS), angiotensinogen (AGT) (M235T), angiotensin converting enzyme (ACE) (insertion/deletion), angiotensin II type 1 receptor (AT1R) (A1166C) and aldosterone synthase (C344T) that are known and might contribute towards the pathophysiology of essential hypertension. Furthermore, the review highlights the response of certain RAAS gene polymorphisms (renin, ACE and AT1R genes) to antihypertensive drugs.

Keywords: ACE; AGT; AT1R genes; essential hypertension; gene polymorphism; renin–angiotensin–aldosterone system.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
RAAS gene polymorphisms. Explanation for the figure: angiotensinogen (AGT) is cleaved by renin to angiotensin I (Ang I), which is further hydrolysed to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). Ang II has two types of receptors: angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R). On one hand, Ang II then binds with AT1R, which directly acts on blood vessels and adrenal glands to increase blood pressure. During this process, aldosterone synthase helps in the secretion of aldosterone that facilitates the reabsorption of sodium and water, thereby increasing BP. On the other hand, AT2R is responsible for vasodilation. There are many gene polymorphisms seen in the RAAS system, such as AGT (M235T), ACE (insertion/deletion) (I/D), Ang II Type 1 receptor (AT1R) (A1166C) and aldosterone synthase (C344T).
Figure 2
Figure 2
Illustration of AT1R (A1166C) gene polymorphism representing a higher prevalence of risk of EH in the patient carrier of the C genotype.
Figure 3
Figure 3
Illustration of antihypertensive drug variance among whites and blacks.
Figure 4
Figure 4
Illustration of variation in drug response among different populations.
See this image and copyright information in PMC

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