title: Examination of genetic variants involved in generation and biodisposition of kinins in patients with angioedema.
abstract: BACKGROUND
  Angioedema (AE) is idiopathic in the majority of cases. We studied patients with AE for genetic variants of proteins involved with bradykinin generation and biodisposition.
  
  
  METHODS
  One hundred sixty one patients with AE were recruited at a university hospital clinic. Patients were categorized according to the proposed pathogenesis of AE: low C1 inhibitor (C1-INH) and C4 levels, autoimmune disease, cancer, angiotensin-converting enzyme (ACE) inhibitor-induced, nonsteroidal antiinflammatory drug (NSAID)-induced, or idiopathic. In addition, each patient had a blood sample analyzed for a complement profile and enzymes (C1-INH and C4). Fifty-two of the patients were tested for genetic variants in factor XII, plasminogen-activator inhibitor-1 (PAI-1), ACE, and aminopeptidase P (APP).
  
  
  RESULTS
  The cause of angioedema was identified in 59/161 (37%) of the cases: 3 (2%) patients had a low plasma C1-INH and C4; 20 (12%) were ACE inhibitor-induced; 12 (7%) were associated with autoimmune disorders; 7 (4%) were associated with malignancy; and 17 (11%) were associated with NSAIDs. In the remaining 102 (63%) patients the cause of angioedema was idiopathic. Of 52 patients with genetic analysis, 13 (25%) had a genetic variant in APP, 10 (19%) in ACE, 13 (25%) in PAI-1, and 0 in Factor XII.
  
  
  CONCLUSIONS
  In addition to related diseases and medications causing AE, certain genetic variants encoding proteins involved in bradykinin generation and/or catabolism pathways may be involved in the pathogenesis of AE.
authors: Division of Dermatology and Cutaneous Sciences, University of Alberta, 2-166 Clinical Sciences Building, 11350 - 83 Avenue, Edmonton, Alberta T6G 2G3 Canada.
authors: Jonathan
authors: J
authors: Levy
authors: CHU Sainte-Justine, Université de Montréal, Montreal, QC Canada.
authors: Georges-Etienne
authors: GE
authors: Rivard
authors: CHU de Québec and UniversitéLaval, Quebec City, QC Canada.
authors: Eric
authors: E
authors: Wagner
authors: National Institute for Occupational Safety and Health, Morgantown, WV Canada.
authors: Don
authors: D
authors: Beezhold
authors: University of Toronto, Toronto, ON Canada.
authors: Noam
authors: N
authors: Berlin
authors: CHU Sainte-Justine, Université de Montréal, Montreal, QC Canada.
authors: Li
authors: L
authors: Fan
authors: CHU Sainte-Justine, Université de Montréal, Montreal, QC Canada.
authors: Zhao
authors: Z
authors: Zhang
authors: University of Toronto, Toronto, ON Canada.
authors: Gordon L
authors: GL
authors: Sussman
keywords: Aminopeptidase P; Angioedema; Angiotensin-converting enzyme; Factor XII; Plasminogen-activator inhibitor-1