{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:01:56Z","timestamp":1787068916972,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,10,20]],"date-time":"2014-10-20T00:00:00Z","timestamp":1413763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["095009, 093727, 080025, 084538"],"award-info":[{"award-number":["095009, 093727, 080025, 084538"]}]},{"name":"Commonwealth Scholarship Commission split-side fellowship","award":["TZCN-2012-361"],"award-info":[{"award-number":["TZCN-2012-361"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>\n                    Fetal hemoglobin (HbF) is a recognized modulator of sickle cell disease (SCD) severity. HbF levels are strongly influenced by genetic variants at three major genetic loci,\n                    <jats:italic>Xmn1\u2010HBG2, HMIP\u20102<\/jats:italic>\n                    , and\n                    <jats:italic>BCL11A<\/jats:italic>\n                    , but the effect of these loci on the hematological phenotype in SCD, has so far not been investigated. In a cohort of individuals with SCD in Tanzania (HbSS and HbS\/\u03b2\u00b0 thalassemia,\n                    <jats:italic>n<\/jats:italic>\n                    = 726, aged 5 or older), HbF levels were positively correlated with hemoglobin, red blood cell (RBC) indices, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), and negatively with white blood cell (WBC) and platelet counts (all\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). We subsequently assessed the contribution of the three HbF modifier loci and detected diverse effects, including a reduction in anemia, leukocytosis, and thrombocytosis associated with certain HbF\u2010promoting alleles. The presence of the \u2018T\u2019 allele at\n                    <jats:italic>Xmn1\u2010HBG2<\/jats:italic>\n                    led to a significant increase in hemoglobin (\n                    <jats:italic>P<\/jats:italic>\n                    = 9.8 \u00d7 10\n                    <jats:sup>\u22123<\/jats:sup>\n                    ) but no changes in cellular hemoglobin content.\n                    <jats:italic>Xmn1\u2010HBG2<\/jats:italic>\n                    \u2018T\u2019 also has a weak effect decreasing WBC (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.06) and platelet (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.06) counts. The\n                    <jats:italic>BCL11A<\/jats:italic>\n                    variant (\n                    <jats:italic>rs11886868<\/jats:italic>\n                    \u2010\u2018C\u2019) increases hemoglobin (\n                    <jats:italic>P<\/jats:italic>\n                    = 2 \u00d7 10\n                    <jats:sup>\u22123<\/jats:sup>\n                    ) and one of the\n                    <jats:italic>HBS1L\u2010MYB<\/jats:italic>\n                    variants decreases WBC values selectively (\n                    <jats:italic>P<\/jats:italic>\n                    = 2.3 \u00d7 10\n                    <jats:sup>\u22124<\/jats:sup>\n                    ). The distinct pattern of effects of each variant suggests that both, disease alleviation through increased HbF production, and \u2018pleiotropic\u2019 effects on blood cells, are involved, affecting a variety of pathways. Am. J. Hematol. 90:E1\u2013E4, 2015. \u00a9 2014 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajh.23859","type":"journal-article","created":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T04:52:59Z","timestamp":1411793579000},"source":"Crossref","is-referenced-by-count":24,"title":["Genetic variants at HbF\u2010modifier loci moderate anemia and leukocytosis in sickle cell disease in\n                    <scp>T<\/scp>\n                    anzania"],"prefix":"10.1002","volume":"90","author":[{"given":"Siana Nkya","family":"Mtatiro","sequence":"first","affiliation":[{"name":"Muhimbili Wellcome Programme Muhimbili University of Health and Allied Sciences Dar\u2010es\u2010Salaam Tanzania"},{"name":"Department of Biological Sciences Dar es Salaam University College of Education, Dar es Salaam  Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Makani","sequence":"additional","affiliation":[{"name":"Muhimbili Wellcome Programme Muhimbili University of Health and Allied Sciences Dar\u2010es\u2010Salaam Tanzania"},{"name":"Nuffield Department of Medicine University of Oxford  United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Mmbando","sequence":"additional","affiliation":[{"name":"Muhimbili Wellcome Programme Muhimbili University of Health and Allied Sciences Dar\u2010es\u2010Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swee Lay","family":"Thein","sequence":"additional","affiliation":[{"name":"Division of Cancer Studies Molecular Haematology, King's College London London United Kingdom"},{"name":"Department of Haematological Medicine King's College Hospital NHS Foundation Trust London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Menzel","sequence":"additional","affiliation":[{"name":"Division of Cancer Studies Molecular Haematology, King's College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon E.","family":"Cox","sequence":"additional","affiliation":[{"name":"Muhimbili Wellcome Programme Muhimbili University of Health and Allied Sciences Dar\u2010es\u2010Salaam Tanzania"},{"name":"Faculty of Epidemiology &amp; Population Health MRC International Nutrition Group, London School of Hygiene &amp; Tropical Medicine London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014699"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406093302303"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp401"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-093419"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11677"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2012.2"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.466"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.531"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.10.005"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.467"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001721-199104000-00018"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2007.1.91"},{"key":"e_1_2_7_14_1","volume-title":"Sickle 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