Abstract 360: Genetic Variants Associated With ACE Inhibitor-Associated Angioedema
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".