Abstract 19037: Impact of the GNB3 C825T Polymorphism on Heart Failure Survival
Bibliographic record
Abstract
Introduction: Genetic background can influence heart failure survival and the impact of therapeutics. A polymorphism of a G protein beta subunit, GNB3 C825T, has been investigated extensively for its impact on the genomic risk of hypertension. The T allele is associated with low renin hypertension and increased alpha adrenergic tone. The T allele is more prevalant in African Americans and in the AHeFT trial was associated with a greater impact of therapy with a fixed dose combination of hydralazine and isosorbide dinitrates. We investigated the impact of GNB3 C825T on transplant free survival in systolic heart failure in GRACE (Genetic Risk Assessment of Cardiac Events), a singe center study based in an outpatient heart failure clinic. Methods: 944 subjects with systolic heart failure were enrolled from the Heart Failure Clinic at the University of Pittsburgh and followed for up to 5 years to an endpoint of death or cardiac transplantation. Demographic information was recorded at the time of enrollment and medical therapy reassessed annually. Blood was obtained at entry for DNA banking, and the GNB3 C825T genotype was determined. Transplant free survival was compared by Kaplan Meier log rank assessment. Results: The cohort was 28% female, 13% black, 48% ischemic, mean age 56 + 9, mean LVEF 0.25 + 0.09, and was NYHA class % 1/2/3/4=4%/52%/40%/4%. In terms of the GNB3 genotype the %TT/TC/CC were 16.5%/41.8%/41.7% and the frequency of the T allele differed significantly by race and was more common in Blacks (p<0.001) . During follow up there were 236 (25%) death, and 126 transplants (13%). The T allele was associated with poor transplant free survival (Figure: p=0.025) driven primarily by poorer absolute survival (p=0.017). Conclusions: The GNB3 825T allele was associated with poorer survival in a cohort with chronic heart failure. Its role in racial differences in heart failure outcomes warrants futher investigation.
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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 | 0.000 | 0.000 |
| 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) | 0.006 | 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".