A Polymorphism in the XPNPEP2 Gene Is Associated with the Development of Hypotensive Transfusion Reactions without ACE Inhibitors.
Bibliographic record
Abstract
Abstract Abstract 3140 Poster Board III-77 Introduction Hypotensive transfusion reactions (HTRs) have been associated with the transfusion of different blood products. They are characterized by the rapid onset and disappearance of hypotension upon starting and finishing the transfusion respectively. The use of ACE inhibitors has been associated with HTRs. However, there are reported HTRs in patients not taking ACE inhibitors. An inability to break down bradykinin (BK) generated during the infusion/transfusion is suggested to be responsible for the hypotensive effect. Angiotensin-converting enzyme (ACE) and aminopeptidase P (APP) are primarily responsible for degradation of BK. We hypothesize that the C-2399A single-nucleotide polymorphism in the membrane-bound APP gene XPNPEP2 (SNP rs3747343) may be linked to HTRs. This polymorphism is present upstream of the coding sequence of the APP gene and has already been associated with severe hypotension in an angioedema patient treated with an ACE inhibitor. This suggests that it may have an important regulatory role. Patients and Methods With the approval of our IRB, patients' samples were collected, de-identified, and then used for testing. Specimens from 4 patients who presented with classic HTRs while not taking ACE inhibitors were analyzed through sequencing of DNA acquired from pre-transfusion blood samples. The same primers were used for PCR and sequencing (5'-GAGTATTATGTGGGGACCATCC-3' and 5'-ATGCCTCGCAGAGACAAGAG-3'). Samples were sequenced in both sense and antisense directions. Results Among these patients, two (50%) were found to possess the C-2399A mutation. One was found to have changes in both reference and complementary strands while the other had a C/A mutation only in one strand. Conclusions These results indicate that the C-2399A polymorphism may be a contributing factor in the development of HTRs and that it may promote HTRs in the absence of ACE inhibitors. The hypotensive effect may be due to a structural or regulatory change caused by C-2399A though it also seems that other factors may be involved since not all patients assayed possessed the mutation. Further screening of additional contributing factors responsible for HTRs is necessary to fully comprehend the pathogenesis of this type of transfusion reaction. Keywords: XPNPEP2, C-2399A, ACE Inhibitors, Hypotensive Transfusion Reactions, aminopeptidase P. Disclosures No relevant conflicts of interest to declare.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 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".