ArticlePloS one2013
Candidate sequence variants and fetal hemoglobin in children with sickle cell disease treated with hydroxyurea.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia.PloS one · 2014Trial
- Evaluation of The Use of Hydroxyurea in Treating Children With Sickle Cell Anemia in Central Africa's Rural Area.EJHaem · 2026Article
- BCL11A and HBS1L-MYB polymorphisms, in association with hydroxyurea and sex, modulate fetal hemoglobin levels in individuals with sickle cell anemia in the western region of Bahia, Brazil.Molecular biology reports · 2026Article
- Genetics and Genomics in Sickle Cell Disease in Africa.American journal of hematology · 2026Review
- Exploring pharmacogenetic factors influencing hydroxyurea response in tanzanian sickle cell disease patients: a genomic medicine approach.The pharmacogenomics journal · 2025Article
- Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea.Haematologica · 2022Article
- Association Between Selected Single Nucleotide Polymorphisms in Globin and Related Genes and Response to Hydroxyurea Therapy in Ghanaian Children with Sickle Cell Disease.Pharmacogenomics and personalized medicine · 2022Article
- Genome-based therapeutic interventions for β-type hemoglobinopathies.Human genomics · 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
- Genetic Modifiers of Fetal Haemoglobin in Sickle Cell Disease.Molecular diagnosis & therapy · 2019Review
- Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism.The pharmacogenomics journal · 2018Review
- Decreased fetal hemoglobin over time among youth with sickle cell disease on hydroxyurea is associated with higher urgent hospital use.Pediatric blood & cancer · 2016Article
- Minireview: Prognostic factors and the response to hydroxurea treatment in sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2016Review
- Variation in Gamma-Globin Expression before and after Induction with Hydroxyurea Associated with BCL11A, KLF1 and TAL1.PloS one · 2015Article
- Article
- Emerging science of hydroxyurea therapy for pediatric sickle cell disease.Pediatric research · 2014Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundFetal hemoglobin level is a heritable complex trait that strongly correlates swith the clinical severity of sickle cell disease. Only few genetic loci have been identified as robustly associated with fetal hemoglobin in patients with sickle cell disease, primarily adults. The sole approved pharmacologic therapy for this disease is hydroxyurea, with effects largely attributable to induction of fetal hemoglobin. METHODOLOGY/PRINCIPAL
findingsIn a multi-site observational analysis of children with sickle cell disease, candidate single nucleotide polymorphisms associated with baseline fetal hemoglobin levels in adult sickle cell disease were examined in children at baseline and induced by hydroxyurea therapy. For baseline levels, single marker analysis demonstrated significant association with BCL11A and the beta and epsilon globin loci (HBB and HBE, respectively), with an additive attributable variance from these loci of 23%. Among a subset of children on hydroxyurea, baseline fetal hemoglobin levels explained 33% of the variance in induced levels. The variant in HBE accounted for an additional 13% of the variance in induced levels, while variants in the HBB and BCL11A loci did not contribute beyond baseline levels. CONCLUSIONS/SIGNIFICANCE: These findings clarify the overlap between baseline and hydroxyurea-induced fetal hemoglobin levels in pediatric disease. Studies assessing influences of specific sequence variants in these and other genetic loci in larger populations and in unusual hydroxyurea responders are needed to further understand the maintenance and therapeutic induction of fetal hemoglobin in pediatric sickle cell disease.
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Registered trials
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