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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,4,21]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The clinical presentation of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    malaria as severe versus uncomplicated is influenced by host genetic factors. Recently, a gain-of-function mutation in the mechanosensitive ion channel\n                    <jats:italic>PIEZO1<\/jats:italic>\n                    was shown to protect mice against cerebral malaria, but its role in human malaria is unknown. Here we investigated a common\n                    <jats:italic>PIEZO1<\/jats:italic>\n                    variant that encodes a mild gain-of-function mutant in human erythrocytes, and show that it is associated with malaria protection in Gabonese children. We found an epistatic relationship between\n                    <jats:italic>PIEZO1<\/jats:italic>\n                    E756del and the sickle cell trait. While parasite growth and cell hydration were normal, surface expression of PfEMP-1 was reduced in the mutant cells. Understanding the link between common\n                    <jats:italic>PIEZO1<\/jats:italic>\n                    variants and malaria susceptibility may yield new therapies for malaria.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1919843117","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T18:15:55Z","timestamp":1586283355000},"page":"9074-9081","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":71,"title":["A common polymorphism in the mechanosensitive ion channel\n                    <i>PIEZO1<\/i>\n                    is associated with protection from severe malaria in humans"],"prefix":"10.1073","volume":"117","author":[{"given":"Christian N.","family":"Nguetse","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Purington","sequence":"additional","affiliation":[{"name":"Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3244-4250","authenticated-orcid":false,"given":"Emily R.","family":"Ebel","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bikash","family":"Shakya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1900-0652","authenticated-orcid":false,"given":"Marilou","family":"Tetard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Kremsner","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany;"},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Albert Schweitzer Hospital, Lambar\u00e9n\u00e9, Gabon;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-9883","authenticated-orcid":false,"given":"Thirumalaisamy P.","family":"Velavan","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany;"},{"name":"Vietnamese-German Center for Medical Research (VG-CARE), Hanoi 113601, Vietnam;"},{"name":"Faculty of Medicine, Duy Tan University, Da Nang 550000, Vietnam;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S.","family":"Egan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305;"},{"name":"Department of Microbiology &amp; Immunology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020340"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.388"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11334"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15390"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1804388115"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/274701a0"},{"key":"e_1_3_3_7_2","first-page":"1","volume-title":"Encyclopedia of Malaria","author":"Nguetse C. 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