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Reduced rate of sickle‐related complications in Brazilian patients carrying HbF‐promoting alleles at the BCL11A and HMIP‐2 loci
Author(s) -
Leonardo Flávia C.,
Brugnerotto Ana F.,
Domingos Igor F.,
Fertrin Kleber Y.,
Albuquerque Dulcinéia M.,
Bezerra Marcos A. C.,
Araújo Aderson S.,
Saad Sara T. O.,
Costa Fernando F.,
Menzel Stephan,
Conran Nicola,
Thein Swee Lay
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13961
Subject(s) - fetal hemoglobin , allele , enhancer , haematopoiesis , biology , myb , hemoglobinopathy , medicine , genetics , transcription factor , immunology , fetus , hemolytic anemia , gene , stem cell , pregnancy
Summary 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 BCL 11A 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.