Association of B2 receptor polymorphisms and ACE activity with ACE inhibitor-induced angioedema in black and mixed-race South Africans

J Clin Hypertens (Greenwich). 2013 Jun;15(6):413-9. doi: 10.1111/jch.12104. Epub 2013 Apr 11.

Abstract

Angiotensin-converting enzyme (ACE) inhibitors are first-line therapy for the treatment of hypertension, congestive heart failure, and diabetic nephropathy. ACE inhibitors are associated with adverse side effects such as persistent dry cough (ACE-cough) and, rarely, life-threatening angioedema (ACE-AE). The authors investigated the influence of ACE I/D polymorphism in combination with serum ACE activity, B₂ receptor -9/+9 polymorphism, and B₂ receptor C-58T single nucleotide polymorphism (SNP) on the development of ACE-AE and ACE-cough. The frequencies of ACE I/D as well as B₂ receptor +9/-9 and C-58T polymorphisms were compared in patients with ACE-AE, ACE-cough, and ACE inhibitor-exposed controls, and serum ACE activity was measured. There were 52 cases of ACE-AE, 36 cases of ACE-cough, and 77 controls. The genotyping revealed a significant association between the B₂ -9 allele and ACE inhibitor-induced AE (62% vs 38%, P=.008), and ACE inhibitor-induced cough (61% vs 38%, P=.02) when compared with controls. There was no significant association between ACE I/D polymorphism as well as the B₂ C-58T SNP with both ACE-induced AE and cough. ACE activity was significantly higher in controls compared with patients with ACE-AE (34.5 ± 1.14 mU/mL vs 17.8 ± 0.86 mU/mL, P=.0001) and ACE-cough (34.5 ± 1.14 mU/mL vs 23.3 ± 1.88 mU/mL, P=.0001). Thus, our data suggest that the B₂ -9 allele and reduced ACE activity are associated with both ACE-AE and ACE-cough.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioedema / chemically induced*
  • Angioedema / genetics
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Black People / genetics*
  • Comorbidity
  • Cough / chemically induced*
  • Cough / genetics
  • Female
  • Genotype
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / ethnology
  • Hypertension / genetics*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Receptor, Bradykinin B2 / genetics*
  • South Africa

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Receptor, Bradykinin B2
  • Peptidyl-Dipeptidase A