ArticleInternational journal of molecular sciences2025
A Lack of Complete Linkage Disequilibrium Between c.1236G>A and c.1129-5923C>G HapB3 Variants of
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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.
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.
Who cites it
1 citing paper in PubMed.
- BioFRAM PGx, an Implementation Proposal for Pharmacogenetics in the Spanish National Health System.Pharmaceuticals (Basel, Switzerland) · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluoropyrimidine derivatives can cause severe toxicity in patients with DPD deficiency. Regulatory agencies, such as the European Medicines Agency (EMA), recommend pre-emptive genotyping of the HapB3 haplotype, along with other variants. Historically, the two main HapB3 variants, the benign c.1236G>A and the pathogenic c.1129-5923C>G, have been assumed to be in complete linkage disequilibrium. Recent findings contradict this assumption, questioning the reliability of the HapB3 analysis through c.1236G>A, which could directly impact patient safety. The aim of this study is to assess the linkage disequilibrium between the c.1236G>A and c.1129-5923C>G variants, with the ultimate goal of revising genotyping guidelines. A total of 46 patients already heterozygous for the c.1236G>A variant have been carefully reviewed for the c.1129-5923C>G variant. From the 46 patients analyzed, 45 maintain complete linkage disequilibrium between both variants. However, there is one patient where this linkage disequilibrium is not complete, being heterozygous for c.1236G>A and homozygous for c.1129-5923C>G. These findings challenge the validity of c.1236G>A as a surrogate marker for pathogenic variant c.1129-5923C>G. This article highlights the need for a review of the recommendations of the EMA and suggests laboratories to analyze both variants, or at least the pathogenic one, to ensure accurate therapeutic decisions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.