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F cell numbers are associated with an X‐linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease
Author(s) -
Urio Florence,
Nkya Siana,
Rooks Helen,
Mgaya Josephine A.,
Masamu Upendo,
Zozimus Sangeda Raphael,
Mmbando Bruno P.,
Brumat Marco,
Mselle Ted,
Menzel Stephan,
Luzzatto Lucio,
Makani Julie
Publication year - 2020
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.17102
Subject(s) - fetal hemoglobin , single nucleotide polymorphism , biology , mean corpuscular volume , locus (genetics) , allele , medicine , snp , genetics , immunology , hemoglobin , gene , genotype , fetus , pregnancy
Summary 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.