In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 60, No. suppl_1 ( 2012-09)
Abstract:
We conducted a genomewide association study in 179 individuals with ACE inhibitor-associated angioedema and 489 ACE inhibitor-exposed controls from Nashville, TN and Marshfield, WI. We performed a replication study in 19 cases and 57 age-, sex-, and ancestry-matched controls from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). There were no genomewide significant associations (p 〈 5x10 -8 ) of any SNP with angioedema in either African or European Americans. Sixteen SNPs in African Americans and 41 SNPs in European Americans that were moderately associated with angioedema (p 〈 10 -4 ) were evaluated for replication in ONTARGET. The T allele of rs500766, a SNP in the gene encoding for protein kinase C θ, was associated with a reduced risk of angioedema in both the Nashville/Marshfield sample (OR 0.42, 95% CI 0.28-0.63, p=2.97x10 -5 in the additive model and OR 0.42, 95% CI 0.26-0.67, p=3.04x10 -4 in the dominant model) and in ONTARGET (OR 0.28, 95% CI 0.09-0.89, p=0.030 in the dominant model). The G allele of rs2724635, a SNP in ETS variant gene 6, was associated with increased risk of ACE inhibitor-associated angioedema in both the Nashville/Marshfield sample (OR 2.78, 95%CI 1.67-4.00, p=2.73x10 -5 in the additive model; OR 3.23, 95%CI 1.75-6.25, p=2.11x10 -4 dominant model; OR 5.56, 95%CI 1.85-16.6, p=2.01x10 -3 recessive mode) and in the ONTARGET sample (OR 3.27, 95%CI 1.03-10.35, p=0.044 in the recessive model). We also conducted a candidate-gene study, using the smaller ONTARGET sample for discovery, and the Nashville/Marshfield study for replication. In the candidate gene study, rs989692 in the gene encoding for neprilysin ( MME ), was significantly associated with angioedema in ONTARGET and in African Americans in the Nashville/Marshfield sample. Variants in genes involved in immune regulation and in neprilysin, an enzyme that degrades bradykinin and substance P, were associated with ACE inhibitor-associated angioedema.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.60.suppl_1.A360
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2012
detail.hit.zdb_id:
2094210-2
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