Evidence map›Paper›PMID 40746153›Full record

SynthesisBritish journal of clinical pharmacology2025

Credibility of genetic predictors for antiepileptic drug resistance: A systematic Bayesian reappraisal of published meta-analyses.

Martina Giacon, Sarah Cargnin, Salvatore Terrazzino

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in British journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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

3 authors.

Martina GiaconDepartment of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.
Sarah CargninDepartment of Health Sciences, University of Piemonte Orientale, Novara, Italy.
Salvatore TerrazzinoDepartment of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.ORCID https://orcid.org/0000-0002-4909-1121

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We systematically reappraised meta-analyses of pharmacogenetic studies to evaluate the credibility of association between gene polymorphisms and resistance to anti-epileptic drugs (AEDs). A systematic search was performed in PubMed, Web of Knowledge, Cochrane Library and OpenGrey up to April 2025. The methodological quality of the included systematic meta-analyses was evaluated with the AMSTAR-2 tool, and the credibility of the genetic comparison results was determined by the Venice criteria and two Bayesian analytic approaches, false positive reporting probability (FPRP), and Bayesian false discovery probability (BFDP). Of the 33 studies identified, 32 were systematic meta-analyses, all of which were rated as critically low quality by AMSTAR-2. Our reassessment indicated seven single nucleotide polymorphisms (SNPs) of four genes-ABCB1 (rs1045642, rs2032582), ABCC2 (rs717620, rs3740066), GABRG2 (rs211037) and SCN1A (rs2298771, rs10167228)-which could be regarded as potential determinants of response to AED. Among these, only ABCB1 rs2032582 (G vs. A and GG vs. GA + AA) was found to be noteworthy in Caucasian epilepsy patients under FPRP or BFDP at the pre-specified probability level of 0.001. However, the application of the Venice criteria to such relationships identified as weak the strength of the cumulative evidence for epidemiological relationship because of a potential publication bias. Our findings, illustrating the poor yield of genetic predictors from meta-analyses of candidate gene studies, underscore the need for large-scale genome-wide association studies (GWAS) and subsequent replication studies for identification of robust predictors of resistance to AEDs.

Indexed as

AnticonvulsantsDrug ResistanceEpilepsyATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BBayes TheoremHumansMeta-Analysis as TopicMultidrug Resistance-Associated Protein 2NAV1.1 Voltage-Gated Sodium ChannelPharmacogeneticsPolymorphism, Single NucleotideABCB1 protein, humanABCC2 protein, humanAnticonvulsantsATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BMultidrug Resistance-Associated Protein 2NAV1.1 Voltage-Gated Sodium ChannelSCN1A protein, humanBFDPdrug responseepilepsyFPRPgene polymorphismsmeta‐analysesVenice criteria

Identifiers

PMID40746153
PMCPMC12464618

What OpenQuestion holds

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LicenceCC BY
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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.