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Record W2782322064 · doi:10.1038/s41397-017-0005-1

Nuclear receptor gene polymorphisms and warfarin dose requirements in the Quebec Warfarin Cohort

2018· article· en· W2782322064 on OpenAlexafffundabout
Payman Shahabi, Félix Lamothe, Stéphanie Dumas, Étienne Rouleau‐Mailloux, Yassamin Feroz Zada, Sylvie Provost, Géraldine Asselin, Ian Mongrain, Diane Valois, Marie-Josée Gaulin Marion, Louis‐Philippe Lemieux Perreault, Sylvie Perreault, Marie‐Pierre Dubé

Bibliographic record

VenueThe Pharmacogenomics Journal · 2018
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacogenetics and Drug Metabolism
Canadian institutionsUniversité de MontréalMontreal Heart Institute
FundersCanadian Institutes of Health Research
KeywordsWarfarinCYP2C9Calcitriol receptorSingle-nucleotide polymorphismNuclear receptorPharmacologyBiologyVKORC1PharmacogeneticsInternal medicinePregnane X receptorGeneMedicineGeneticsGenotypeTranscription factorAtrial fibrillation

Abstract

fetched live from OpenAlex

Warfarin is primarily metabolized by cytochrome 2C9, encoded by gene CYP2C9 . Here, we investigated whether variants in nuclear receptor genes which regulate the expression of CYP2C9 are associated with warfarin response. We used data from 906 warfarin users from the Quebec Warfarin Cohort (QWC) and tested the association of warfarin dose requirement at 3 months following the initiation of therapy in nine nuclear receptor genes: NR1I3, NR1I2, NR3C1, ESR1, GATA4, RXRA, VDR, CEBPA , and HNF4A . Three correlated SNPs in the VDR gene (rs4760658, rs11168292, and rs11168293) were associated with dose requirements of warfarin ( P = 2.68 × 10 −5 , P = 5.81 × 10 −4 , and P = 5.94 × 10 −4 , respectively). Required doses of warfarin were the highest for homozygotes of the minor allele at the VDR variants ( P < 0.0026). Variants in the VDR gene were associated with the variability in response to warfarin, emphasizing the possible clinical relevance of nuclear receptor gene variants on the inter-individual variability in drug metabolism.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.124
Threshold uncertainty score0.250

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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.

Opus teacher head0.119
GPT teacher head0.411
Teacher spread0.292 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations6
Published2018
Admission routes3
Has abstractyes

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