Fetal-haemoglobin enhancing genotype at BCL11A reduces HbA 2 levels in patients with sickle cell anaemia

Understanding the interplay of genetic factors with haemoglobin expression and pathological processes in sickle cell disease is important for pharmacological and gene-therapeutic interventions. In our nascent study cohort of Nigerian patients, we found that three major disease-modifying factors, HbF...

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Published inEJHaem Vol. 2; no. 3; pp. 459 - 461
Main Authors Adeyemo, Titilope A, Ojewunmi, Oyesola O, Oyetunji, Idayat Ajoke, Kalejaiye, Olufunto Olufela, Menzel, Stephan
Format Journal Article
LanguageEnglish
Published United States 01.08.2021
Subjects
African patient population
genetic analysis
BCL11A
HbA
sickle cell disease
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Abstract Understanding the interplay of genetic factors with haemoglobin expression and pathological processes in sickle cell disease is important for pharmacological and gene-therapeutic interventions. In our nascent study cohort of Nigerian patients, we found that three major disease-modifying factors, HbF levels, α-thalassaemia deletion and genotype, had expected beneficial haematological effects. A key variant, while improving HbF levels (5.7%-9.0%), also led to a small, but significant decrease in HbA . We conclude that in general, interventions boosting HbF are likely to reduce HbA in patients' erythroid cells and that such therapeutic strategies might benefit from a parallel stimulation of HbA through independent mechanisms.
AbstractList Understanding the interplay of genetic factors with haemoglobin expression and pathological processes in sickle cell disease is important for pharmacological and gene-therapeutic interventions. In our nascent study cohort of Nigerian patients, we found that three major disease-modifying factors, HbF levels, α-thalassaemia deletion and genotype, had expected beneficial haematological effects. A key variant, while improving HbF levels (5.7%-9.0%), also led to a small, but significant decrease in HbA . We conclude that in general, interventions boosting HbF are likely to reduce HbA in patients' erythroid cells and that such therapeutic strategies might benefit from a parallel stimulation of HbA through independent mechanisms.
Abstract Understanding the interplay of genetic factors with haemoglobin expression and pathological processes in sickle cell disease is important for pharmacological and gene‐therapeutic interventions. In our nascent study cohort of Nigerian patients, we found that three major disease‐modifying factors, HbF levels, α‐thalassaemia deletion and BCL11A genotype, had expected beneficial haematological effects. A key BCL11A variant, while improving HbF levels (5.7%–9.0%), also led to a small, but significant decrease in HbA 2 . We conclude that in general, interventions boosting HbF are likely to reduce HbA 2 in patients’ erythroid cells and that such therapeutic strategies might benefit from a parallel stimulation of HbA 2 through independent mechanisms.
Author Ojewunmi, Oyesola O
Kalejaiye, Olufunto Olufela
Menzel, Stephan
Adeyemo, Titilope A
Oyetunji, Idayat Ajoke
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Cites_doi 10.1371/journal.pone.0197927
10.1007/s40291-018-0370-8
10.1111/j.1749-6632.1969.tb27776.x
10.1002/ajh.23811
10.1093/clinchem/42.7.1113
10.1073/pnas.90.11.5039
10.1111/j.1365-2141.1987.tb01343.x
10.1371/journal.pone.0111464
10.1056/NEJM198202043060504
10.1182/blood.V63.6.1353.1353
10.1126/science.804182
10.1073/pnas.76.2.670
10.1007/s00277-020-04079-2
10.1159/000203622
10.1002/ajh.23859
10.1111/bjh.12084
10.1186/1471-2326-11-2
10.1056/NEJM198206173062402
10.1111/j.1365-2141.1993.tb04639.x
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Keywords African patient population
genetic analysis
BCL11A
HbA
sickle cell disease
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Embury SH (e_1_2_7_14_1) 1994
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  doi: 10.1371/journal.pone.0197927
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  doi: 10.1002/ajh.23811
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  doi: 10.1093/clinchem/42.7.1113
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  volume-title: Sickle cell disease: basic principles and clinical practice
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  doi: 10.1126/science.804182
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  doi: 10.1073/pnas.76.2.670
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  doi: 10.1007/s00277-020-04079-2
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  doi: 10.1159/000203622
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  doi: 10.1002/ajh.23859
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  doi: 10.1111/bjh.12084
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  doi: 10.1186/1471-2326-11-2
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  doi: 10.1056/NEJM198206173062402
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