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Record W2333350059 · doi:10.2337/db15-1247

Variation in <i>SLC19A3</i> and Protection From Microvascular Damage in Type 1 Diabetes

2015· article· en· W2333350059 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueDiabetes · 2015
Typearticle
Languageen
FieldMedicine
TopicAlcoholism and Thiamine Deficiency
Canadian institutionsHospital for Sick Children
FundersNational Institute of Neurological Disorders and StrokeWilhelm och Else Stockmanns StiftelseNational Eye InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesSigne ja Ane Gyllenbergin SäätiöNovo Nordisk FondenAcademy of FinlandNational Institutes of HealthFolkhälsanin TutkimussäätiöTekesFinska LäkaresällskapetSuomen Kulttuurirahasto
KeywordsRetinopathySingle-nucleotide polymorphismMedicineNephropathyInternal medicineDiabetes mellitusGenome-wide association studyEndocrinologyLinkage disequilibriumType 2 diabetesCohortDiabetic retinopathyType 1 diabetesGenetic associationBiologyGeneticsGenotypeGene

Abstract

fetched live from OpenAlex

The risk of long-term diabetes complications is not fully explained by diabetes duration or long-term glycemic exposure, suggesting the involvement of genetic factors. Because thiamine regulates intracellular glucose metabolism and corrects for multiple damaging effects of high glucose, we hypothesized that variants in specific thiamine transporters are associated with risk of severe retinopathy and/or severe nephropathy because they modify an individual's ability to achieve sufficiently high intracellular thiamine levels. We tested 134 single nucleotide polymorphisms (SNPs) in two thiamine transporters (SLC19A2/3) and their transcription factors (SP1/2) for an association with severe retinopathy or nephropathy or their combination in the FinnDiane cohort. Subsequently, the results were examined for replication in the DCCT/EDIC and Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) cohorts. We found two SNPs in strong linkage disequilibrium in the SLC19A3 locus associated with a reduced rate of severe retinopathy and the combined phenotype of severe retinopathy and end-stage renal disease. The association for the combined phenotype reached genome-wide significance in a meta-analysis that included the WESDR cohort. These findings suggest that genetic variations in SLC19A3 play an important role in the pathogenesis of severe diabetic retinopathy and nephropathy and may explain why some individuals with type 1 diabetes are less prone than others to develop microvascular complications.

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.

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)0.000
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.159
Threshold uncertainty score0.362

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 head0.022
GPT teacher head0.236
Teacher spread0.215 · 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