Associations between <b><i>TNFAIP3</i></b> Polymorphisms and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis Update with Trial Sequential Analysis
Bibliographic record
Abstract
INTRODUCTION: The tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene produces ubiquitin-editing protein A20, which inhibits nuclear factor-κB (NF-κB) activation in a variety of signaling pathways. We examined the association between TNFAIP3 polymorphisms and rheumatoid arthritis (RA) susceptibility. METHODS: MEDLINE, Embase, Scopus, and Web of Science were searched for available articles on TNFAIP3 polymorphisms in RA patients from inception until July 11, 2022. We included case-control studies on the association between rs2230926 and rs5029937 polymorphisms of TNFAIP3 and RA, and we excluded studies that contained overlapping data. We scored the quality of each study included based on the Newcastle-Ottawa Scale. Meta-analyses evaluated the association between TNFAIP3 polymorphisms and RA susceptibility in diverse ethnic populations and was verified through trial sequential analysis (TSA). This meta-analysis was registered in the PROSPERO register (number: CRD42022345160). There was no funding source. RESULTS: Seventeen studies were chosen for meta-analysis. Ten studies for rs2230926, and seven for rs5029937. An association was noted between TNFAIP3 rs2230926 G allele and RA in all subjects (odds ratio [OR] = 1.389; 95% confidence interval [CI] = 1.161-1.662; p < 0.001). Ethnicity-specific analysis showed significant association of rs2230926 G allele with RA in Europeans and Asians (OR = 1.642; 95% CI = 1.099-2.452; p = 0.015; OR = 1.404; 95% CI = 1.262-1.562; p < 0.001). An association was also noted between TNFAIP3 rs5029937 T allele and RA in all subjects (OR = 1.389; 95% CI = 1.207-1.785; p < 0.001). An ethnicity-specific meta-analysis revealed a significant association of the rs5029937 T allele with RA in Europeans and Asians. Dominant model analysis showed the same pattern for TNFAIP3 rs2230926 G and rs5029937 T alleles in Europeans and Asians, suggesting an association between rs2230926 G and rs5029937. TSA indicated a robust association between the TNFAIP3 polymorphisms and the risk of RA. CONCLUSION: TNFAIP3 rs2230926 and rs5029937 polymorphisms are associated with RA susceptibility in European and Asian populations. However, the data were not stratified by parameters such as rheumatoid factor status, disease activity, or environmental variables.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.027 | 0.053 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.020 | 0.032 |
| Bibliometrics | 0.006 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".