{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:23:56Z","timestamp":1770704636261,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\/Aga Khan","award":["n\u00ba330842553"],"award-info":[{"award-number":["n\u00ba330842553"]}]},{"name":"FCT\/Aga Khan","award":["UIDB\/05608\/2020"],"award-info":[{"award-number":["UIDB\/05608\/2020"]}]},{"name":"FCT\/Aga Khan","award":["UIDP\/05608\/2020"],"award-info":[{"award-number":["UIDP\/05608\/2020"]}]},{"name":"FCT\/MCTES\u2013H&amp;TRC","award":["n\u00ba330842553"],"award-info":[{"award-number":["n\u00ba330842553"]}]},{"name":"FCT\/MCTES\u2013H&amp;TRC","award":["UIDB\/05608\/2020"],"award-info":[{"award-number":["UIDB\/05608\/2020"]}]},{"name":"FCT\/MCTES\u2013H&amp;TRC","award":["UIDP\/05608\/2020"],"award-info":[{"award-number":["UIDP\/05608\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The aim of this study was to identify genetic markers in the HBB Cluster; HBS1L-MYB intergenic region; and BCL11A, KLF1, FOX3, and ZBTB7A genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hematological, biochemical, and clinical data were considered to determine patients\u2019 severity phenotypes. Samples from 192 patients were sequenced, and 5,019,378 variants of high quality were registered. A catalog of candidate modifier genes that clustered in pathophysiological pathways important for SCA was generated, and candidate genes associated with increasing vaso-occlusive crises (VOC) and with lower fetal hemoglobin (HbF) were identified. These data support the polygenic view of the genetic architecture of SCA phenotypic variability. Two single nucleotide polymorphisms in the intronic region of 2q16.1, harboring the BCL11A gene, are genome-wide and significantly associated with decreasing HbF. A set of variants was identified to nominally be associated with increasing VOC and are potential genetic modifiers harboring phenotypic variation among patients. To the best of our knowledge, this is the first investigation of clinical variation in SCA in Angola using a well-customized and targeted sequencing approach.<\/jats:p>","DOI":"10.3390\/genes15040469","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T10:11:55Z","timestamp":1712571115000},"page":"469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Modifiers of Sickle Cell Anemia Phenotype in a Cohort of Angolan Children"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-782X","authenticated-orcid":false,"given":"Catarina","family":"Ginete","sequence":"first","affiliation":[{"name":"H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Sa\u00fade, Instituto Polit\u00e9cnico de Lisboa, 1990-096 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0586-9154","authenticated-orcid":false,"given":"Mariana","family":"Delgadinho","sequence":"additional","affiliation":[{"name":"H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Sa\u00fade, Instituto Polit\u00e9cnico de Lisboa, 1990-096 Lisbon, Portugal"}]},{"given":"Br\u00edgida","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola (CISA), Bengo 9999, Angola"},{"name":"Hospital Pedi\u00e1trico David Bernardino (HPDB), Luanda 3067, Angola"}]},{"given":"Armandina","family":"Miranda","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge (INSA), 1649-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1021-7935","authenticated-orcid":false,"given":"Carina","family":"Silva","sequence":"additional","affiliation":[{"name":"H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Sa\u00fade, Instituto Polit\u00e9cnico de Lisboa, 1990-096 Lisbon, Portugal"},{"name":"Centro de Estat\u00edstica e Aplica\u00e7\u00f5es, Universidade de Lisboa, 1649-013 Lisbon, Portugal"}]},{"given":"Paulo","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Sa\u00fade, Instituto Polit\u00e9cnico de Lisboa, 1990-096 Lisbon, Portugal"}]},{"given":"Emile R.","family":"Chimusa","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-658X","authenticated-orcid":false,"given":"Miguel","family":"Brito","sequence":"additional","affiliation":[{"name":"H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Sa\u00fade, Instituto Polit\u00e9cnico de Lisboa, 1990-096 Lisbon, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola (CISA), Bengo 9999, Angola"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle cell disease","volume":"4","author":"Kato","year":"2018","journal-title":"Nat. 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