Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci

Flávia C. Leonardo; Ana F. Brugnerotto; Igor F. Domingos; Kleber Y. Fertrin; Dulcinéia M. de Albuquerque; Marcos A C Bezerra; Aderson S. Araújo; Sara T O Saad; Fernando F. Costa; Stephan Menzel; Nicola Conran; Swee Lay Thein

doi:10.1111/bjh.13961

Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci

Flávia C. Leonardo^*, Ana F. Brugnerotto, Igor F. Domingos, Kleber Y. Fertrin, Dulcinéia M. de Albuquerque, Marcos A C Bezerra, Aderson S. Araújo, Sara T O Saad, Fernando F. Costa, Stephan Menzel, Nicola Conran, Swee Lay Thein

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke.

Original language	English
Pages (from-to)	456-460
Number of pages	5
Journal	British Journal of Haematology
Volume	173
Issue number	3
DOIs	https://doi.org/10.1111/bjh.13961
Publication status	Published - May 2016

Keywords

BCL11A
HbF quantitative trait loci
HMIP-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/bjh.13961

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Leonardo, F. C., Brugnerotto, A. F., Domingos, I. F., Fertrin, K. Y., de Albuquerque, D. M., Bezerra, M. A. C., Araújo, A. S., Saad, S. T. O., Costa, F. F., Menzel, S., Conran, N., & Thein, S. L. (2016). Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci. British Journal of Haematology, 173(3), 456-460. https://doi.org/10.1111/bjh.13961

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title = "Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci",

abstract = "The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke.",

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author = "Leonardo, {Fl{\'a}via C.} and Brugnerotto, {Ana F.} and Domingos, {Igor F.} and Fertrin, {Kleber Y.} and {de Albuquerque}, {Dulcin{\'e}ia M.} and Bezerra, {Marcos A C} and Ara{\'u}jo, {Aderson S.} and Saad, {Sara T O} and Costa, {Fernando F.} and Stephan Menzel and Nicola Conran and Thein, {Swee Lay}",

year = "2016",

month = may,

doi = "10.1111/bjh.13961",

language = "English",

volume = "173",

pages = "456--460",

journal = "British Journal of Haematology",

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Leonardo, FC, Brugnerotto, AF, Domingos, IF, Fertrin, KY, de Albuquerque, DM, Bezerra, MAC, Araújo, AS, Saad, STO, Costa, FF, Menzel, S, Conran, N & Thein, SL 2016, 'Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci', British Journal of Haematology, vol. 173, no. 3, pp. 456-460. https://doi.org/10.1111/bjh.13961

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AU - Leonardo, Flávia C.

AU - Brugnerotto, Ana F.

AU - Domingos, Igor F.

AU - Fertrin, Kleber Y.

AU - de Albuquerque, Dulcinéia M.

AU - Bezerra, Marcos A C

AU - Araújo, Aderson S.

AU - Saad, Sara T O

AU - Costa, Fernando F.

AU - Menzel, Stephan

AU - Conran, Nicola

AU - Thein, Swee Lay

PY - 2016/5

Y1 - 2016/5

N2 - The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke.

AB - The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke.

KW - BCL11A

KW - HbF quantitative trait loci

KW - HMIP-2

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ER -

Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci

Abstract

Keywords

UN SDGs

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