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Record W2557587008 · doi:10.1194/jlr.p065250

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

2016· article· en· W2557587008 on OpenAlexaff
Latisha Love‐Gregory, Aldi T. Kraja, Fiona Allum, Stella Aslibekyan, Åsa K. Hedman, Yanan Duan, Ingrid B. Borecki, Donna K. Arnett, Mark I. McCarthy, Panos Deloukas, José M. Ordovás, Paul N. Hopkins, Elin Grundberg, Nada A. Abumrad

Bibliographic record

VenueJournal of Lipid Research · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPeroxisome Proliferator-Activated Receptors
Canadian institutionsMcGill University and Génome Québec Innovation Centre
FundersNational Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteCooperative State Research, Education, and Extension ServiceNational Institutes of HealthNational Institute for Health and Care ResearchLonger Life FoundationGeorgia Clinical and Translational Science AllianceBroad InstituteHarvard UniversityAmerican Heart Association
KeywordsChylomicronCD36PostprandialDNA methylationSingle-nucleotide polymorphismBiologyMethylationLipid metabolismPromoterInternal medicineEndocrinologyGeneticsGene expressionLipoproteinGeneGenotypeCholesterolMedicineVery low-density lipoprotein

Abstract

fetched live from OpenAlex

Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined the effects of SNPs within a ∼410 kb region encompassing CD36 and its proximal and distal promoters on chylomicron (CM) remnants and LDL particles at fasting and at 3.5 and 6 h following a high-fat meal (Genetics of Lipid Lowering Drugs and Diet Network study, n = 1,117). Five promoter variants associated with CMs, four with delayed TG clearance and five with LDL particle number. To assess mechanisms underlying the associations, we queried expression quantitative trait loci, DNA methylation, and ChIP-seq datasets for adipose and heart tissues that function in postprandial lipid clearance. Several SNPs that associated with higher serum lipids correlated with lower adipose and heart CD36 mRNA and aligned to active motifs for PPARγ, a major CD36 regulator. The SNPs also associated with DNA methylation sites that related to reduced CD36 mRNA and higher serum lipids, but mixed-model analyses indicated that the SNPs and methylation independently influence CD36 mRNA. The findings support contributions of CD36 SNPs that reduce adipose and heart CD36 RNA expression to inter-individual variability of postprandial lipid metabolism and document changes in CD36 DNA methylation that influence both CD36 expression and lipids.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.038
Threshold uncertainty score0.300

Codex and Gemma teacher scores by category

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

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 head0.055
GPT teacher head0.339
Teacher spread0.284 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations37
Published2016
Admission routes1
Has abstractyes

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