ArticleBMC medical genomics2025
Novel LRF/ZBTB7A variants and known HbF-modulating SNPs in transfusion-dependent β-thalassemia.
Article in BMC medical genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
backgroundβ-Thalassemia is a hereditary blood disorder with a highly variable clinical presentation that is partly influenced by genetic modifiers that regulate fetal hemoglobin levels. Elevated HbF can ameliorate the clinical symptoms of β-thalassemia, making the identification of HbF-modifying loci crucial for understanding disease variability and developing potential therapeutic strategies.
methodsIn this study, we evaluated the distribution and effect of known HbF-associated single nucleotide polymorphisms within the BCL11A, HMIP, and XmnI-HBG2 loci in β-thalassemia patients. Our investigation was initiated by a hypothesis based on genomic data from the K562 cell line, which indicated the presence of a specific LRF/ZBTB7A variant. In addition, we explored the role of LRF/ZBTB7A, a transcription factor implicated in globin gene regulation, through Sanger sequencing and in silico analyses. A hypothetical Genetic Modifier Score was devised to quantify the cumulative effect of the five major HbF-associated QTLs.
resultsWhile we confirmed the previously reported associations of the common SNPs with HbF levels, we also identified novel rare variants in LRF/ZBTB7A (p.Pro241Leu, p.Asp344Asp, p.Glu277del) that may influence HbF expression. XmnI-HBG2 accounted for a small yet significant proportion (7%) of HbF variability. A significant positive correlation was found between the Genetic Modifier Score and HbF levels, yet the model explained only ~ 14% of the variance, highlighting a substantial role for other modifiers such as the novel LRF/ZBTB7A variants identified here.
conclusionsThese results suggest LRF/ZBTB7A is a novel modifier of HbF. The discovery of the variants, against a backdrop of modest QTL effects, underscores its potential and warrants further functional investigation.
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.