Association of B2 Receptor Polymorphisms and ACE Activity With ACE Inhibitor-Induced Angioedema in Black and Mixed-Race South Africans

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 +/- 1.14mU/mL vs 17.8 +/- 0.86mU/mL, P=.0001) and ACE-cough (34.5 +/- 1.14mU/mL vs 23.3 +/- 1.88mU/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. (C) 2013 Wiley Periodicals, Inc.