{"doi":"10.1101/2022.08.02.501704","title":"Non- <i>O</i> ABO blood group genotypes differ in their associations with <i>Plasmodium falciparum</i> rosetting and severe malaria","abstract":"Abstract Blood group O is associated with protection against severe malaria and reduced size and stability of P. falciparum- host red blood cell (RBC) rosettes compared to non-O blood groups. Whether the non-O blood groups encoded by the specific ABO genotypes AO, BO, AA, BB and AB differ in their associations with severe malaria and rosetting is unknown. The A and B antigens are host RBC receptors for rosetting, hence we hypothesized that the higher levels of A and/or B antigen on RBCs from AA, BB and AB genotypes compared to AO/BO genotypes could lead to larger rosettes, increased microvascular obstruction and higher risk of malaria pathology. We used a case-control study of Kenyan children and in vitro adhesion assays to test the hypothesis that “double dose” non- O genotypes ( AA, BB, AB ) are associated with increased risk of severe malaria and larger rosettes than “single dose” heterozygotes ( AO, BO ). In the case-control study, compared to OO , the double dose genotypes consistently had higher odds ratios (OR) for severe malaria than single dose genotypes, with AB (OR 1.93) and AO (OR 1.27) showing most marked difference (P=0.02, Wald test). In vitro experiments with blood group A-preferring P. falciparum parasites showed that significantly larger rosettes were formed with AA and AB host RBCs compared to OO , whereas AO genotype rosettes were indistinguishable from OO . Overall, the data show that ABO genotype influences P. falciparum rosetting and support the hypothesis that double dose non- O genotypes confer a greater risk of severe malaria than AO/BO heterozygosity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303973,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":530847,"name":"Carolyne Ndila","orcid":"0000-0002-5694-3652","position":1,"is_corresponding":false},{"id":827873,"name":"Sophie Uyoga","orcid":"0000-0003-1746-7873","position":2,"is_corresponding":false},{"id":654403,"name":"Alex Macharia","orcid":null,"position":3,"is_corresponding":false},{"id":996824,"name":"Clare Fennell","orcid":null,"position":4,"is_corresponding":false},{"id":919681,"name":"Gideon Nyutu","orcid":"0000-0002-5984-7690","position":5,"is_corresponding":false},{"id":996391,"name":"John Ojal","orcid":"0000-0002-3010-1158","position":6,"is_corresponding":false},{"id":996825,"name":"Mohammed Shebe","orcid":null,"position":7,"is_corresponding":false},{"id":996826,"name":"Kennedy O. Awuondo","orcid":null,"position":8,"is_corresponding":false},{"id":919682,"name":"Neema Mturi","orcid":"0000-0002-6585-2074","position":9,"is_corresponding":false},{"id":642005,"name":"Norbert Peshu","orcid":"0000-0002-8038-3894","position":10,"is_corresponding":false},{"id":843635,"name":"Benjamin Tsofa","orcid":"0000-0003-1000-1771","position":11,"is_corresponding":false},{"id":94993,"name":"Gavin Band","orcid":"0000-0002-1710-9024","position":12,"is_corresponding":false},{"id":827877,"name":"Kathryn Maitland","orcid":"0000-0002-0007-0645","position":13,"is_corresponding":false},{"id":33751,"name":"Dominic Kwiatkowski","orcid":"0000-0002-5023-0176","position":14,"is_corresponding":false},{"id":62202,"name":"Kirk A. Rockett","orcid":"0000-0002-6369-9299","position":15,"is_corresponding":false},{"id":530852,"name":"Thomas N. Williams","orcid":"0000-0003-4456-2382","position":16,"is_corresponding":false},{"id":729009,"name":"J. 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