Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia
PublishereLife Sciences Publications Ltd
MetadataShow full item record
AbstractMalaria 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.
Identifier to cite or link to this itemhttps://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
- Human genetic polymorphisms in the Knops blood group are not associated with a protective advantage against Plasmodium falciparum malaria in Southern Ghana.
- Authors: Hansson HH, Kurtzhals JA, Goka BQ, Rodriques OP, Nkrumah FN, Theander TG, Bygbjerg IC, Alifrangis M
- Issue date: 2013 Nov 7
- Complement receptor 1 polymorphisms associated with resistance to severe malaria in Kenya.
- Authors: Thathy V, Moulds JM, Guyah B, Otieno W, Stoute JA
- Issue date: 2005 Nov 8
- No Evidence that Knops Blood Group Polymorphisms Affect Complement Receptor 1 Clustering on Erythrocytes.
- Authors: Swann OV, Harrison EM, Opi DH, Nyatichi E, Macharia A, Uyoga S, Williams TN, Rowe JA
- Issue date: 2017 Dec 19
- Identification of complement receptor one (CR1) polymorphisms in west Africa.
- Authors: Moulds JM, Kassambara L, Middleton JJ, Baby M, Sagara I, Guindo A, Coulibaly S, Yalcouye D, Diallo DA, Miller L, Doumbo O
- Issue date: 2000 Jun
- Red blood cell complement receptor one level varies with Knops blood group, α(+)thalassaemia and age among Kenyan children.
- Authors: Opi DH, Uyoga S, Orori EN, Williams TN, Rowe JA
- Issue date: 2016 Apr