F cell numbers are associated with an X-linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease.

Autor: Urio F; Muhimbili Sickle Cell Programme, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.; Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania., Nkya S; Muhimbili Sickle Cell Programme, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.; Department of Biological Sciences, Dar es salaam University College of Education, University of Dar es Salaam, Dar es Salaam, Tanzania., Rooks H; Comprehensive Cancer Centre, Kings College London, London, UK., Mgaya JA; Muhimbili Sickle Cell Programme, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania., Masamu U; Muhimbili Sickle Cell Programme, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania., Zozimus Sangeda R; Muhimbili Sickle Cell Programme, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.; Department of Pharmaceutical Microbiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania., Mmbando BP; Muhimbili Sickle Cell Programme, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.; National Institute for Medical Research, Tanga, Tanzania., Brumat M; Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy., Mselle T; Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania., Menzel S; Comprehensive Cancer Centre, Kings College London, London, UK., Luzzatto L; Department of Haematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania., Makani J; Muhimbili Sickle Cell Programme, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.; Department of Haematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2020 Dec; Vol. 191 (5), pp. 888-896. Date of Electronic Publication: 2020 Oct 19.
DOI: 10.1111/bjh.17102
Abstrakt: Patients with sickle cell disease (SCD) with high fetal haemoglobin (HbF) tend to have a lower incidence of complications and longer survival due to inhibition of deoxyhaemoglobin S (HbS) polymerisation by HbF. HbF-containing cells, namely F cells, are strongly influenced by genetic factors. We measured the percentage of F cells (Fcells%) in 222 patients with SCD to evaluate the association of (i) Fcells% with genetic HbF-modifier variants and (ii) Fcells% with haematological parameters. There was a different distribution of Fcells% in females compared to males. The association of the B-cell lymphoma/leukaemia 11A (BCL11A) locus with Fcells% (β = 8·238; P < 0·001) and with HbF% (β = 2·490; P < 0·001) was significant. All red cell parameters except for Hb and mean corpuscular Hb concentration levels in males and females were significantly different. The Fcells% was positively associated with mean cell Hb, mean cell volume and reticulocytes. To explain the significant gender difference in Fcells%, we tested for associations with single nucleotide polymorphisms on the X chromosomal region Xp22.2, where a genetic determinant of HbF had been previously hypothesised. We found in males a significant association with a SNP in FERM and PDZ domain-containing protein 4 (FRMPD4) and adjacent to male-specific lethal complex subunit 3 (MSL3). Thus, we have identified an X-linked locus that could account for a significant fraction of the Fcells% variation in patients with SCD.
(© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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