{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T23:24:06Z","timestamp":1780788246093,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T00:00:00Z","timestamp":1603065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>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\u2010containing 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\u2010modifier variants and (ii) Fcells% with haematological parameters. There was a different distribution of Fcells% in females compared to males. The association of the B\u2010cell lymphoma\/leukaemia 11A (<jats:italic>BCL11A<\/jats:italic>) locus with Fcells% (\u03b2\u00a0=\u00a08\u00b7238; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001) and with HbF% (\u03b2\u00a0=\u00a02\u00b7490; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001) 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\u2010containing protein 4 (<jats:italic>FRMPD4<\/jats:italic>) and adjacent to male\u2010specific lethal complex subunit 3 (<jats:italic>MSL3<\/jats:italic>). Thus, we have identified an X\u2010linked locus that could account for a significant fraction of the Fcells% variation in patients with SCD.<\/jats:p>","DOI":"10.1111\/bjh.17102","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T15:07:58Z","timestamp":1603120078000},"page":"888-896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["F cell numbers are associated with an X\u2010linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease"],"prefix":"10.1111","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3241-9768","authenticated-orcid":false,"given":"Florence","family":"Urio","sequence":"first","affiliation":[{"name":"Muhimbili Sickle Cell Programme Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"},{"name":"Department of Biochemistry Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siana","family":"Nkya","sequence":"additional","affiliation":[{"name":"Muhimbili Sickle Cell Programme Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"},{"name":"Department of Biological Sciences Dar es salaam University College of Education University of Dar es Salaam Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Rooks","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Centre Kings College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine A.","family":"Mgaya","sequence":"additional","affiliation":[{"name":"Muhimbili Sickle Cell Programme Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upendo","family":"Masamu","sequence":"additional","affiliation":[{"name":"Muhimbili Sickle Cell Programme Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Zozimus Sangeda","sequence":"additional","affiliation":[{"name":"Muhimbili Sickle Cell Programme Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"},{"name":"Department of Pharmaceutical Microbiology Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno P.","family":"Mmbando","sequence":"additional","affiliation":[{"name":"Muhimbili Sickle Cell Programme Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"},{"name":"National Institute for Medical Research Tanga Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Brumat","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences University of Trieste Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Mselle","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-9108","authenticated-orcid":false,"given":"Stephan","family":"Menzel","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Centre Kings College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4663-8790","authenticated-orcid":false,"given":"Lucio","family":"Luzzatto","sequence":"additional","affiliation":[{"name":"Department of Haematology and Blood Transfusion Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Makani","sequence":"additional","affiliation":[{"name":"Muhimbili Sickle Cell Programme Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"},{"name":"Department of Haematology and Blood Transfusion Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406093302303"},{"key":"e_1_2_10_3_1","unstructured":"SteinbergMH ForgetBG HiggsDR WeatherallDJ.Disorders of Hemoglobin[Internet].Cambridge:Cambridge University Press;2009[cited 2019 Sep 11]. 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