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It is highly prevalent in sub-Saharan Africa, especially in Angola, where SCA and malaria are major causes of childhood mortality. This study aimed to explore whether genetic variants in genes associated with red blood cell adhesion to the vascular endothelium influence the manifestations of SCA in Angolan pediatric patients in the context of malaria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      The study enrolled 65 pediatric SCA patients living in Luanda or Caxito. Their clinical, hematological, and biochemical profiles were monitored through longitudinal pediatric follow-up appointments. Fifteen polymorphic sites were genotyped in\n                      <jats:italic>CD36<\/jats:italic>\n                      and\n                      <jats:italic>ICAM-1<\/jats:italic>\n                      genes using PCR, Sanger sequencing, and fragment analysis by capillary electrophoresis. Malaria infection was evaluated by detecting\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      species DNA through PCR analysis of blood spot samples. The\n                      <jats:italic>CD36<\/jats:italic>\n                      variant rs3211891_C is revealed for the first time as a potential modulator of anemia severity in SCA. Additionally, the\n                      <jats:italic>CD36<\/jats:italic>\n                      variant rs3211938_G, along with the\n                      <jats:italic>ICAM-1<\/jats:italic>\n                      variants rs5491_T and rs5496_A, significantly impacted the severity of the hematological phenotype in SCA. Furthermore, SCA patients carrying the\n                      <jats:italic>ICAM-1<\/jats:italic>\n                      rs5494_T variant showed a 5.63-fold increased risk of having malaria infection compared to those with the wild-type genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study enhances our understanding of genetic modifiers of red blood cell adhesion to the vascular endothelium and their influence on the severity of pediatric SCA in the context of frequent concomitant malaria infection in Angola.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-026-12029-w","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:56:45Z","timestamp":1779973005000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic variants in red blood cell adhesion-related genes influence the severity of sickle cell anemia in a malaria-endemic region"],"prefix":"10.1007","volume":"53","author":[{"given":"Irina","family":"Matos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Br\u00edgida","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elis\u00e2ngela","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Brito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Arez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6269-4867","authenticated-orcid":false,"given":"Paula","family":"Faustino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"issue":"16","key":"12029_CR1","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1056\/NEJMra1510865","volume":"376","author":"FB Piel","year":"2017","unstructured":"Piel FB, Steinberg MH, Rees DC (2017) Sickle Cell Disease. 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