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Title: PGRN-RIKEN: Identification of Genetic Predictors of ACE Inhibitor-Associated Angioedema      
citations:
17085287
8689816
18025295
17531305
description:
The purpose of this study is to identify genetic predictors of ACE inhibitor-associated angioedema. In addition to preventing the formation of the pressor angiotensin II, ACE inhibitors prevent the carboxyl-terminal degradation of the vasoactive substances bradykinin and substance P. Angioedema is hypothesized to result from defective amino-terminal degradation of bradykinin or substance P in patients in whom ACE is inhibited. For example, activity of dipeptidyl peptidase IV (DPP-IV), the enzyme responsible for the inactivation of substance P when ACE is inhibited, is decreased in patients with angioedema. In preliminary studies, we have identified SNPs in the DPP4 gene that associate with DPP-IV activity and, in blacks, with risk of angioedema. This project will use genome-wide genotyping to compare 250 cases and 568 ACE inhibitor-exposed control subjects (131 cases and 288 controls ascertained at Vanderbilt and 70 cases and 280 controls ascertained at the Marshfield Clinic). We plan a 2-stage analysis of associations between SNPs and angioedema - first, we will study DPP4 SNPs for association with angioedema and, second, we will explore associations using the full GWAS data set. Depending on the platform, additional DPP4 SNPs will be used to fully tag common genetic variants in both African American and European American samples. Based on the HapMap data, there are 14 tagging SNPs in people of European descent and 34 in Yoruba (selection criteria MAF>0.05 and r2>0.8). Cases were defined as having ACE inhibitor-associated angioedema if they had had swelling of the lips, throat, tongue or face while taking an ACE inhibitor but had never had angioedema while not taking an ACE inhibitor. For simplicity, intestinal edema was excluded. Control subjects were treated for at least 6 months with an ACE inhibitor without angioedema. Because black Americans are known to be overrepresented among patients with ACE inhibitor-associated angioedema, control subjects were prespecified to be 50% black American, 50% white American, and 50% female. At Vanderbilt, the medical history, including the history of angioedema, was confirmed by a research nurse or physician using a detailed case report form. Characteristics of Vanderbilt cases appear in the Table. At Marshfield, medical history will be confirmed by chart review. The Marshfield cohort is 98% white American and 57% female with a mean age of 47.2 years.
Identifier:
phs000438.v1.p1
accesstypes:
download
enclave
landingpage: http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000438.v1.p1
authentication: simpleLogin
none
authorization:
none
duaIndividual
name:
Angioedema
affiliations:
Vanderbilt University Medical Center, Nashville, TN, USA
name:
Nancy Brown, MD
roles:
Principal Investigator
affiliations:
Vanderbilt University Medical Center, Nashville, TN, USA
name:
Vanderbilt University PGRN Group (PAT)
roles:
Institute
performedBy:
TitleNameInstitute Principal InvestigatorNancy Brown, MDVanderbilt University Medical Center, Nashville, TN, USA InstituteVanderbilt University PGRN Group (PAT)Vanderbilt University Medical Center, Nashville, TN, USA
downloadURL: https://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?page=DUC&view_pdf&stacc=phs000438.v1.p1
Identifier:
phs000438.v1.p1_policy
name:
Data Use Certificate
Identifier:
1
name:
Health/Medical/Biomedical
alternateIdentifiers:
yes
selectionCriteria:

Inclusion criteria

Cases: 1) Men or women age 18 or older; 2) African- or Caucasian-Americans; 3) With angioedema, defined by swelling of the lips, tongue, pharynx, or face while taking an ACE inhibitor.

Controls: 1) Men or women age 18 or older; 2) African- or Caucasian-Americans; 3) Taken and ACE inhibitor for at least 6 months and never experienced angioedema; 4) May include subjects who experienced cough.

Exclusion criteria for all subjects

1) History of angioedema while not taking an ACE inhibitor; 2) Angioedema only involves the bowel; 3) Decreased C1 inhibitor or complement concentrations; 4) Mental conditions which render the subject unable to understand the nature, scope, and possible consequences of the study.

types:
Case-Control
dateReleased:
11-25-2011
version:
phs000438.v1.p1
dateModified:
05-28-2013
abbreviation:
NHLBI
name:
National Heart, Lung, and Blood Institute DAC
ID:
0
name:
dbGaP

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