Evidence map›Paper›PMID 41653417›Full record

SynthesisHaemophilia : the official journal of the World Federation of Hemophilia

TNF‑α Gene Polymorphisms as Determinants of Alloantibody Emergence in Hemophilia: A Systematic Review and Meta-Analysis.

Alessandra Faustino da Conceição Bezerra, Natã Abner Andrade Carito de Sousa, Suely Meireles Rezende, Renan Pedra de Souza

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Haemophilia : the official journal of the World Federation of Hemophilia. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Alessandra Faustino da Conceição BezerraLaboratório De Biologia Integrativa, Grupo De Pesquisa em Bioestatística e Epidemiologia Molecular, Departamento De Genética, Ecologia e Evolução, Instituto De Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Natã Abner Andrade Carito de SousaLaboratório De Biologia Integrativa, Grupo De Pesquisa em Bioestatística e Epidemiologia Molecular, Departamento De Genética, Ecologia e Evolução, Instituto De Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Suely Meireles RezendeDepartamento De Clínica Médica, Faculdade De Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Belo Horizonte, Brazil.
Renan Pedra de SouzaLaboratório De Biologia Integrativa, Grupo De Pesquisa em Bioestatística e Epidemiologia Molecular, Departamento De Genética, Ecologia e Evolução, Instituto De Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Funding

Conselho Nacional de Desenvolvimento Científico e TecnológicoCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundação de Amparo à Pesquisa do Estado de Minas Gerais
6 · The paper itself

Abstract

introductionInhibitor development remains one of the most serious complications of replacement therapy in patients with hemophilia. Tumour necrosis factor-alpha (TNF-α) is a key pro-inflammatory cytokine, and its genetic variants have been implicated in immune-related conditions. The association between TNF-α gene polymorphisms and inhibitor formation in hemophilia has been explored.

aimTo systematically review and quantitatively synthesize available evidence on the association between TNF-α gene polymorphisms and the development of inhibitors in patients with hemophilia.

methodsA comprehensive literature search was conducted in PubMed and SciELO from inception to 11 February 2025. Eligible studies evaluated TNF-α polymorphisms in patients with hemophilia and reported data on inhibitor status. Data extraction and quality assessment (using the Q-Genie tool) were performed independently by two reviewers. Meta-analyses were conducted using the Mantel-Haenszel method, where pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

resultsNineteen studies met the inclusion criteria for the systematic review, and ten were included in the meta-analysis. A significant association was observed between the rs1800629 (-308G>A) polymorphism and inhibitor development under the A-recessive model (OR = 2.00; 95% CI: 1.13-3.54). No significant associations were found for other TNF-α polymorphisms.

conclusionThis meta-analysis suggests that the TNF-α rs1800629 polymorphism may be associated with an increased risk of inhibitor development in patients with hemophilia. These findings highlight the potential role of inflammatory genetic variants in modulating the immune response to replacement therapy. Further large-scale, multi-ethnic studies are needed to confirm these results and better understand the underlying mechanisms.

Indexed as

Hemophilia AIsoantibodiesPolymorphism, GeneticPolymorphism, Single NucleotideTumor Necrosis Factor-alphaGenetic Predisposition to DiseaseHumansIsoantibodiesTumor Necrosis Factor-alphacytokinegenetic associationimmune responseinhibitor developmentpro‐inflammatory

Identifiers

PMID41653417
PMCPMC13175436

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.