Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia.
Elife
; 72018 04 25.
Article
en En
| MEDLINE
| ID: mdl-29690995
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 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
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Malaria Cerebral
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Receptores de Complemento 3b
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Talasemia alfa
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
País como asunto:
Africa
Idioma:
En
Año:
2018
Tipo del documento:
Article