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RAS Genetic Variants in Interaction with ACE Inhibitors Drugs Influences Essential Hypertension Control

Farzad Heidari1, Ramachandran Vasudevan2, Siti Zubaidah Mohd Ali3

  • 1Department of Biomedical Science, Genetic Research Group, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM Serdang Selangor, Malaysia.

Archives of Medical Research
|June 5, 2017
PubMed

Insights

Genetic variations in the renin-angiotensin-aldosterone system (RAS) impact essential hypertension control in patients treated with angiotensin-converting enzyme inhibitors (ACEI). Specific RAS gene polymorphisms correlate with blood pressure reduction in hypertensive individuals.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Essential Hypertension (EH) is a prevalent condition in Malaysia, contributing to significant cardiovascular morbidity and mortality.
  • The Renin-Angiotensin-Aldosterone System (RAS) plays a crucial role in blood pressure regulation and is a target for antihypertensive therapies.

Purpose of the Study:

  • To investigate the influence of genetic polymorphisms within the RAS on the efficacy of Angiotensin-Converting Enzyme Inhibitor (ACEI) drugs in controlling Essential Hypertension.
  • To identify specific RAS gene variants associated with differential blood pressure responses to ACEI monotherapy.

Main Methods:

  • A case-control, cross-sectional, population-based nested study involving 142 hypertensive subjects treated with ACEI monotherapy (lisinopril or enalapril) for 24 weeks.
  • Genotyping of seven potential polymorphisms in key RAS genes, including ACE, AGT, and renin.
  • Analysis of the association between identified polymorphisms and changes in systolic and diastolic blood pressure post-treatment.

Main Results:

  • Statistically significant associations were found between specific alleles (I, G, T, M, G) of ACE and AGT genes and essential hypertension.
  • Patients with II, GG, and TT genotypes in ACE (I/D), AGT (M235T), and AGT (T175M) respectively showed greater reductions in systolic and diastolic blood pressure compared to other genotypes.
  • No significant association was observed between renin gene polymorphisms (Bg/I and MboI) and hypertension control in this cohort.

Conclusions:

  • The study suggests a potential link between RAS gene polymorphisms and the risk of uncontrolled hypertension in patients receiving ACEI treatment.
  • These findings highlight the importance of various RAS components in hypertension regulation and underscore the need for further validation in larger, diverse populations.
Abstract

Keywords:
EnalaprilGene polymorphismLisinoprilPharmacogenetics HypertensionRenin-angiotensin-aldosterone System

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