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    Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia

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    Author
    Swann, O.
    Macharia, A.
    Date
    2018
    Journal
    eLife
    Publisher
    eLife Sciences Publications Ltd
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.7554/eLife.31579
    Abstract
    Malaria has been a major driving force in the evolution of the human genome. In sub-Saharan African populations, two neighbouring polymorphisms in the Complement Receptor One (CR1) gene, named Sl2 and McC b , occur at high frequencies, consistent with selection by malaria. Previous studies have been inconclusive. Using a large case-control study of severe malaria in Kenyan children and statistical models adjusted for confounders, we estimate the relationship between Sl2 and McC b and malaria phenotypes, and find they have opposing associations. The Sl2 polymorphism is associated with markedly reduced odds of cerebral malaria and death, while the McC b polymorphism is associated with increased odds of cerebral malaria. We also identify an apparent interaction between Sl2 and α+thalassaemia, with the protective association of Sl2 greatest in children with normal a-globin. The complex relationship between these three mutations may explain previous conflicting findings, highlighting the importance of considering genetic interactions in disease-association studies. Copyright Opi et al.
    Keyword
    Malaria, Cerebral
    Polymorphism, Genetic
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85051842826&doi=10.7554%2feLife.31579&partnerID=40&md5=0f89c5f5be71a1aedd36d23e993c622f; http://hdl.handle.net/10713/9742
    ae974a485f413a2113503eed53cd6c53
    10.7554/eLife.31579
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