ArticleAnnals of hematology2020
Functional polymorphisms of BCL11A and HBS1L-MYB genes affect both fetal hemoglobin level and clinical outcomes in a cohort of children with sickle cell anemia.
Article in Annals of hematology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Global genetic modifiers of fetal hemoglobin in sickle cell disease: Systematic review and meta-analysis.iScience · 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
- Genetic polymorphism of SNPs rs9399137 and rs4895441in HBS1L-MYB and SNP rs766432 in BCL11A among β-thalassemia Egyptian patients.BMC genomic data · 2026Article
- A genetic risk score based on BCL11A and HBS1L-MYB variants predicts clinical severity in Brazilian sickle cell anaemia patients.British journal of haematology · 2026Article
- Systematic Review of Non-Coding Genomic Variants in Globin and Non-Globin Clusters and Their Impact on Phenotypic Severity in Thalassemia and Sickle Cell Disease.Journal of clinical medicine · 2026Review
- Review
- Genetic Modifiers Associated with Vaso-Occlusive Crises and Acute Pain Phenomena in Sickle Cell Disease: A Scoping Review.International journal of molecular sciences · 2025Article
- Transcriptional regulators of fetal hemoglobin.Hematology, transfusion and cell therapy · 2024Review
- Article
- Article
- Fetal hemoglobin level predicts lower-risk myelodysplastic syndrome.International journal of hematology · 2023Article
- Effect of haplotypes of functional SNPs related to expression of fetal hemoglobin (HbF) on clinical prognosis of hematological malignancies.International journal of hematology · 2023Article
- Role of microRNA in hydroxyurea mediated HbF induction in sickle cell anaemia patients.Scientific reports · 2023Article
- Fetal hemoglobin-boosting haplotypes of BCL11A gene and HBS1L-MYB intergenic region in the prediction of clinical and hematological outcomes in a cohort of children with sickle cell anemia.Journal of human genetics · 2022Article
- Fetal-haemoglobin enhancing genotype atEJHaem · 2021Article
- Genotypic Diversity among Angolan Children with Sickle Cell Anemia.International journal of environmental research and public health · 2021Article
- Evolutionary history of sickle-cell mutation: implications for global genetic medicine.Human molecular genetics · 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
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Fetal hemoglobin (HbF) ameliorates clinical severity of sickle cell anemia (SCA). The major loci regulating HbF levels are HBB cluster, BCL11A, and HMIP-2 (HBS1L-MYB). However, the impact of noncoding single-nucleotide polymorphisms (SNPs) in these loci on clinical outcomes and their functional role on regulating HbF levels should be better elucidated. Therefore, we performed comprehensive association analyses of 14 noncoding SNPs in five loci with HbF levels and with clinical outcomes in a cohort of 250 children with SCA from Southeastern Brazil, and further performed functional annotation of these SNPs. We found SNPs independently associated with HbF levels: rs4671393 in BCL11A (β-coefficient = 0.28), rs9399137 in HMIP-2A (β-coefficient = 0.16), and rs4895441 in HMIP-2B (β-coefficient = 0.15). Patients carrying minor (HbF-boosting) alleles for rs1427407, rs93979137, rs4895441, rs9402686, and rs9494145 showed reduced count of reticulocytes (p < 0.01), while those carrying the T allele of rs9494145 showed lower white blood cell count (p = 0.002). Carriers of the minor allele for rs9402686 showed higher peripheral saturation of oxygen (p = 0.002). Patients carrying minor alleles in BCL11A showed lower risk of transfusion incidence rate ratio (IRR ≥ 1.3; p < 0.0001). This effect was independent of HbF effect (p = 0.005). Carriers of minor alleles for rs9399137 and rs9402686 showed lower risk of acute chest syndrome (IRR > 1.3; p ≤ 0.01). Carriers of the reference allele for rs4671393 showed lower risk of infections (IRR = 1.16; p = 0.01). In conclusion, patients carrying HbF-boosting alleles of BCL11A and HMIP-2 were associated with milder clinical phenotypes. Higher HbF concentration may underlie this effect.
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