Trial reportPloS one2014
Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Practical guide for disease-modifying medication management of children and adolescents with sickle cell disease.Hematology. American Society of Hematology. Education Program · 2024Guideline
- Role ofLife (Basel, Switzerland) · 2025Article
- Exploring pharmacogenetic factors influencing hydroxyurea response in tanzanian sickle cell disease patients: a genomic medicine approach.The pharmacogenomics journal · 2025Article
- Beyond Ischemia: The Rare Occurrence of Hemorrhagic Strokes in Pediatric Sickle Cell Anemia.Cureus · 2024Article
- Towards genomic medicine: a tailored next-generation sequencing panel for hydroxyurea pharmacogenomics in Tanzania.BMC medical genomics · 2024Article
- Are Genetic Modifiers the Answer to Different Responses to Hydroxyurea Treatment?-A Pharmacogenetic Study in Sickle Cell Anemia Angolan Children.International journal of molecular sciences · 2023Article
- Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea.Haematologica · 2022Article
- Techniques for the Detection of Sickle Cell Disease: A Review.Micromachines · 2021Review
- Do Genetic Polymorphisms Affect Fetal Hemoglobin (HbF) Levels in Patients With Sickle Cell Anemia Treated With Hydroxyurea? A Systematic Review and Pathway Analysis.Frontiers in pharmacology · 2021Review
- Article
- Whole-exome sequencing indicatesExperimental biology and medicine (Maywood, N.J.) · 2019Article
- Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism.The pharmacogenomics journal · 2018Review
- Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells.Blood · 2018Article
- A Retrospective Analysis of Sociodemographic and Hematologic Characteristics Associated With Achieving Optimal Hydroxyurea Therapy in Children With Sickle Cell Disease.Journal of pediatric hematology/oncology · 2018Article
- Whole-exome sequencing of sickle cell disease patients with hyperhemolysis syndrome suggests a role for rare variation in disease predisposition.Transfusion · 2018Article
- Pharmacogenomics of sickle cell disease: steps toward personalized medicine.Pharmacogenomics and personalized medicine · 2017Review
- Study on Hydroxyurea Response in Hemoglobinopathies Patients Using Genetic Markers and Liquid Erythroid Cultures.Hematology reports · 2016Article
- The role of BCL11A and HMIP-2 polymorphisms on endogenous and hydroxyurea induced levels of fetal hemoglobin in sickle cell anemia patients from southern Brazil.Blood cells, molecules & diseases · 2016Article
- Minireview: Prognostic factors and the response to hydroxurea treatment in sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2016Review
- Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular Filtration Rate in Children with Sickle Cell Anemia.PloS one · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final %HbF minus baseline %HbF), and final %HbF. Analyzing individual genetic variants, we identified multiple low frequency and common variants associated with HbF induction by hydroxyurea. A validation cohort of 130 pediatric sickle cell patients treated to MTD with hydroxyurea was genotyped for 13 non-synonymous variants with the strongest association with HbF response to hydroxyurea in the discovery cohort. A coding variant in Spalt-like transcription factor, or SALL2, was associated with higher final HbF in this second independent replication sample and SALL2 represents an outstanding novel candidate gene for further investigation. These findings may help focus future functional studies and provide new insights into the pharmacological HbF upregulation by hydroxyurea in patients with SCA.
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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.