eLife · 2018
Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Opi D Herbert, Swann Olivia, Macharia Alexander, Uyoga Sophie, Band Gavin, Ndila Carolyne M, Harrison Ewen M, Thera Mahamadou A, Kone Abdoulaye K, Diallo Dapa A, Doumbo Ogobara K, Lyke Kirsten E, Plowe Christopher V, Moulds Joann M, Shebbe Mohammed, Mturi Neema, Peshu Norbert, Maitland Kathryn, Raza Ahmed, Kwiatkowski Dominic P, Rockett Kirk A, Williams Thomas N, Rowe J Alexandra
Аннотация
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 McCb, 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 McCb 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 McCb 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 α-globin. The complex relationship between these three mutations may explain previous conflicting findings, highlighting the importance of considering genetic interactions in disease-association studies.