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Record W2523064628 · doi:10.1089/omi.2016.0119

<i>SLCO1B1</i> Gene Variations Among Tanzanians, Ethiopians, and Europeans: Relevance for African and Worldwide Precision Medicine

2016· article· en· W2523064628 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.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueOMICS A Journal of Integrative Biology · 2016
Typearticle
Languageen
FieldMedicine
TopicTuberculosis Research and Epidemiology
Canadian institutionsnot available
FundersEuropean and Developing Countries Clinical Trials PartnershipAddis Ababa UniversityKarolinska InstitutetCentre in Green Chemistry and Catalysis
KeywordsSLCO1B1HaplotypePharmacogeneticsGenotypeMedicineAlleleOrganic anion transporter 1GeneGeneticsPharmacologyBioinformaticsBiologyTransporter

Abstract

fetched live from OpenAlex

The solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encodes for a membrane-bound organic anion transporter protein involved in active cellular influx of many endogenous compounds and xenobiotics. SLCO1B1 genetic variation is associated, for example, with highly variable rifampicin exposure, thus influencing the cornerstone antituberculosis therapy, especially in sub-Saharan Africa where it is a key therapeutic modality. Yet, there is no SLCO1B1-guided pharmacogenetic dosing recommendation for rifampicin to reduce the risk of adverse events or therapy failure. Accordingly, comparative characterization of SLCO1B1, particularly within understudied African populations, is crucial and timely for global precision medicine, given the importance of antituberculosis therapy worldwide. Therefore, we report here the allele, genotype, and haplotype frequencies for common SLCO1B1 gene polymorphisms among Europeans (N = 57), Tanzanians (N = 361), and Ethiopians (N = 632). Our results show that the allele frequencies of rs4149032T, rs2306283G, rs11045819A, and rs4149056C differ significantly among Ethiopians (48.1%, 60.3%, 2.8%, 19.1%). Tanzanians (51.9%, 86.8%, 4.7%, 3.2%), and Europeans (19.8%, 34.2%, 7.9%, 22.8%) (p < 0.001). Notably, the most common haplotypes in Tanzanians (TGCT; g.38664T + c.388G + c.463C + c.521T = 61.1%) and Europeans (CGCT, all wild-type SLCO1B*1A = 59.8%) occurred at a much lower frequency in Ethiopians (TGCT = 38.8% and CGCT = 31.6%) (p < 0.0001). Additionally, the nonfunctional SLCO1B1 haplotypes CGCC (*15) and CACC (*5) are relatively common or detectable in Ethiopians (14.1%, 3.2%, respectively) and Europeans (18.1%, 2.8%) but rare in Tanzanians (1.9% and 0%, respectively) (p < 0.001). These new observations collectively underscore that precision medicine for rifampicin and other cornerstone therapeutics will require a comparative study of each and every population in the African continent as well as globally. SLCO1B1 and its extensive within- and between-population variations have to be carefully borne in mind for global precision medicine.

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)0.002
metaresearch head score (Gemma)0.011
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.692
Threshold uncertainty score0.997

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.011
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
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 head0.026
GPT teacher head0.331
Teacher spread0.305 · 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