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Ninety-six donors representing homozygotes (carriers of the minor alleles, T\/T (variant), heterozygote T\/C and wildtype C\/C (ancestral)) carriers of the tagging SNP rs1541252 were selected from a cohort of over 12,000 participants in the Keneba Biobank.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Red blood cells (RBCs) from homozygotes showed reduced PMCA4b protein expression (mean fluorescence intensities (MFI\u2009=\u20092428\u2009\u00b1\u2009124, 3544\u2009\u00b1\u2009159 and 4261\u2009\u00b1\u2009283], for homozygotes, heterozygotes and wildtypes respectively, p\u2009&lt;\u20090.0001) and slower rates of calcium expulsion (calcium t\n                      <jats:sub>\u00bd<\/jats:sub>\n                      \u2009\u00b1\u2009SD\u2009=\u20094.7\u2009\u00b1\u20090.5, 1.8\u2009\u00b1\u20090.3 and 1.9\u2009\u00b1\u20090.4\u00a0min, p\u2009&lt;\u20090.0001). Growth of a\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      laboratory strain (FCR3) and two Gambian field isolates was decreased in RBCs from homozygotes compared to heterozygotes and wildtypes (p\u2009&lt;\u20090.01). Genotype group did not affect parasite adhesion in vitro or\n                      <jats:italic>var<\/jats:italic>\n                      -gene expression in malaria-infected RBCs. Parasite growth was inhibited by a known inhibitor of PMCA4b, aurintricarboxylic acid (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u2009122uM CI: 110\u2013134) confirming its sensitivity to calcium channel blockade.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The data support the hypothesis that this\n                      <jats:italic>ATP2B4<\/jats:italic>\n                      genotype, common in The Gambia and other malaria-endemic areas, protects against severe malaria through the suppression of parasitaemia during an infection. Reduction in parasite density plays a pivotal role in disease outcome by minimizing all aspects of malaria pathogenesis. Follow up studies are needed to further elucidate the mechanism of protection and to determine if this\n                      <jats:italic>ATP2B4<\/jats:italic>\n                      genotype carries a fitness cost or increases susceptibility to other human disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-022-04359-4","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T16:03:37Z","timestamp":1672934617000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults"],"prefix":"10.1186","volume":"22","author":[{"given":"Fatou","family":"Joof","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Jarvis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alhassan","family":"Colley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"Cross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Avril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Prentice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Cerami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"4359_CR1","unstructured":"WHO. 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