title: Association of B2 receptor polymorphisms and ACE activity with ACE inhibitor-induced angioedema in black and mixed-race South Africans.
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.
authors.affiliation: Division of Medical Biochemistry, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Retsilisitsoe R
authors.initials: RR
authors.lastname: Moholisa
authors.forename: Brian R
authors.initials: BR
authors.lastname: Rayner
authors.forename: E
authors.initials: E
authors.lastname: Patricia Owen
authors.forename: Sylva L U
authors.initials: SL
authors.lastname: Schwager
authors.forename: Joalice S
authors.initials: JS
authors.lastname: Stark
authors.forename: Motassim
authors.initials: M
authors.lastname: Badri
authors.forename: Clint L
authors.initials: CL
authors.lastname: Cupido
authors.forename: Edward D
authors.initials: ED
authors.lastname: Sturrock
mesh_terms: D000368:Aged; D000799:Angioedema / Q000139:chemically induced* / Q000235:genetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D044383:Black People / Q000235:genetics*; D015897:Comorbidity; D003371:Cough / Q000139:chemically induced* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D043782:Receptor, Bradykinin B2 / Q000235:genetics*; D013019:South Africa
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D043782:Receptor, Bradykinin B2; D007703:Peptidyl-Dipeptidase A