Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia
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, suggesting selection by malaria. Previous studies have been incon...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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eLife Sciences Publications
2018
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| _version_ | 1797088639120834560 |
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| author | Herbert Opi, D Swann, O Macharia, A Uyoga, S Band, G Ndila, C Harrison, E Thera, M Kone, A Diallo, D Doumbo, O Lyke, K Plowe, C Moulds, J Shebe, M Mturi, N Peshu, N Maitland, K Raza, A Kwiatkowski, D Rockett, K Williams, T Rowe, A |
| author_facet | Herbert Opi, D Swann, O Macharia, A Uyoga, S Band, G Ndila, C Harrison, E Thera, M Kone, A Diallo, D Doumbo, O Lyke, K Plowe, C Moulds, J Shebe, M Mturi, N Peshu, N Maitland, K Raza, A Kwiatkowski, D Rockett, K Williams, T Rowe, A |
| author_sort | Herbert Opi, D |
| collection | OXFORD |
| description | 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, suggesting 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 demonstrate that Sl2 and McCb have opposing malaria 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 identified an unexpected interaction between Sl2 and α+thalassaemia, revealing that the protective association of Sl2 was greatest in children with normal α-globin. The complex relationship between these three mutations may explain previous conflicting findings, and the data highlight the importance of considering genetic interactions in disease-association studies. |
| first_indexed | 2024-03-07T02:52:58Z |
| format | Journal article |
| id | oxford-uuid:ae4f1a8e-5dde-464f-93d3-3495e31eac11 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:52:58Z |
| publishDate | 2018 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:ae4f1a8e-5dde-464f-93d3-3495e31eac112022-03-27T03:41:45ZTwo complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ae4f1a8e-5dde-464f-93d3-3495e31eac11Symplectic Elements at OxfordeLife Sciences Publications2018Herbert Opi, DSwann, OMacharia, AUyoga, SBand, GNdila, CHarrison, EThera, MKone, ADiallo, DDoumbo, OLyke, KPlowe, CMoulds, JShebe, MMturi, NPeshu, NMaitland, KRaza, AKwiatkowski, DRockett, KWilliams, TRowe, AMalaria 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, suggesting 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 demonstrate that Sl2 and McCb have opposing malaria 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 identified an unexpected interaction between Sl2 and α+thalassaemia, revealing that the protective association of Sl2 was greatest in children with normal α-globin. The complex relationship between these three mutations may explain previous conflicting findings, and the data highlight the importance of considering genetic interactions in disease-association studies. |
| spellingShingle | Herbert Opi, D Swann, O Macharia, A Uyoga, S Band, G Ndila, C Harrison, E Thera, M Kone, A Diallo, D Doumbo, O Lyke, K Plowe, C Moulds, J Shebe, M Mturi, N Peshu, N Maitland, K Raza, A Kwiatkowski, D Rockett, K Williams, T Rowe, A Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia |
| title | Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia |
| title_full | Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia |
| title_fullStr | Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia |
| title_full_unstemmed | Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia |
| title_short | Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia |
| title_sort | two complement receptor one alleles have opposing associations with cerebral malaria and interact with α thalassaemia |
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