Correlation of renin angiotensin system (RAS) candidate gene polymorphisms with response to Ramipril in patients with essential hypertension

J Postgrad Med. 2015 Jan-Mar;61(1):21-6. doi: 10.4103/0022-3859.147028.


Background: The renin-angiotensin system (RAS) is an important facet of blood pressure regulation physiology. Treatment of essential hypertension targets the RAS using Angiotensin Converting Enzyme Inhibitors (ACEIs). However, ACEIs are not uniformly effective and show inter-individual pharmacodynamic variations.

Aim: To assess the correlation between genetic polymorphisms in the genes coding for RAS components (angiotensin converting enzyme (ACE I/D), α-adducin (ADD1) and β1 -adrenoreceptor (β1-ADR)) and response to Ramipril.

Materials and methods: We recruited 120 patients with essential hypertension who were administered Ramipril monotherapy initially, followed by combination therapy, if needed, based on their responses. Relationship between genotypes of the three candidate genes and decrease in the blood pressure (BP) was analyzed.

Results: One hundred and six patients were evaluable at the end of the study period and 21 different genotypes were observed among them. Seven of them were classified as responders after 8 weeks and at the end of 12 weeks, an additional 77 (72.64%) were deemed responders. 19/22 non-responders were treated with combination therapy and 7/19 (36.84%) showed a response to the same. There was a significant difference between the proportions of responders and non-responders among the genotypes of the ADD1 and β1-ADR genes (P=0.005 and 0.003, respectively). The best predictors of response to Ramipril 5 mg daily were the II/GG/SS, II/TG/SS, II/GG/SG, ID/GG/SS, ID/GG/SG and ID/TT/SS and DD/GG/SS; II/GG/GG, II/TT/SG, ID/TG/SG, ID/TT/SG, DD/GG/SG and DD/GG/GG were moderately predictive and II/TT/SS, II/TG/GG, ID/TG/GG, DD/TG/SG and DD/TG/GG were poorly predictive of response.

Discussion: Variable responses to Ramipril may be the result of genetic factors.

Conclusion: Pre-prescription genotyping may help individualize treatment.

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Calmodulin-Binding Proteins / genetics*
  • Essential Hypertension
  • Female
  • Genotype
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Ramipril / pharmacology*
  • Ramipril / therapeutic use
  • Renin-Angiotensin System / genetics*
  • Treatment Outcome


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Calmodulin-Binding Proteins
  • adducin
  • Peptidyl-Dipeptidase A
  • Ramipril