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Record W2903191393 · doi:10.3389/fphar.2018.01390

Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population

2018· article· en· W2903191393 on OpenAlexaff
Shuang Lv, Huizhen Fan, Li Jiang, Hui Yang, Jing Huang, Xiaoming Shu, Lu Zhang, Yuan Xu, Xiaoya Li, Jieyu Zuo, Cheng Xiao

Bibliographic record

VenueFrontiers in Pharmacology · 2018
Typearticle
Languageen
FieldMedicine
TopicRheumatoid Arthritis Research and Therapies
Canadian institutionsUniversity of Alberta
FundersChina-Japan Friendship HospitalBeijing Friendship Hospital, Capital Medical UniversityBeijing University of Chinese MedicineNational Natural Science Foundation of China
KeywordsMTRRMethylenetetrahydrofolate reductaseInternal medicineMedicineRheumatoid arthritisSingle-nucleotide polymorphismGastroenterologyMethotrexateGenotypeGeneticsGeneBiology

Abstract

fetched live from OpenAlex

Objective: Analysis of the relationship between single nucleotide polymorphisms (SNPs) and outcomes of methotrexate (MTX) therapy for rheumatoid arthritis (RA) in China. Patients and methods: TYMS 28 bp VNTR (rs34743033), MTHFR (677C>T (rs1801133) and 1298A>C (rs1801131)), ATIC 347C>G (rs2372536), MTR A2756G (rs1805087) and MTRR 66A>G (rs1801394) enzyme proteins may be related to the outcomes of MTX therapy, according to our previous meta-analysis. A total of 162 patients with RA were included in our study. SNPs were evaluated using polymerase chain reaction (PCR). Disease Activity Score 28 (DAS28) was used to evaluate the clinical response, and adverse drug reactions (ADRs) were collected after physical examinations of the patients. Results: The MTHFR 677C>T gene showed a relationship with the ADRs of MTX in the Recessive model (TT vs (CC+CT)) (p=0.04, OR=2.20, 95% CI: 1.01, 4.77). In the Codominant model (CT vs (CC+TT)), the MTHFR 677C>T gene also showed a trend of association with ADRs (p=0.08, OR=0.52, 95% CI: 0.25, 1.08). No significant difference was found between TYMS, MTHFR, ATIC, MTR and MTRR gene polymorphisms and the RA response or ADRs related to MTX in our study. Conclusion: Our results showed that the MTHFR (677C>T (rs1801133) TT genotype is associated with ADRs to MTX in Chinese RA patients. Other SNPs, including TYMS 28bp VNTR (rs34743033), MTHFR (677C>T (rs1801133) and 1298A>C (rs1801131)), ATIC 347C>G (rs2372536), MTR A2756G (rs1805087) and MTRR 66A>G (rs1801394) gene polymorphisms, were not associated with MTX treatment outcomes. Further studies are required to validate these findings.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.063
Threshold uncertainty score0.461

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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 head0.015
GPT teacher head0.331
Teacher spread0.316 · 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 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

Citations27
Published2018
Admission routes1
Has abstractyes

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