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Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α + thalassaemia.
- Source :
-
ELife [Elife] 2018 Apr 25; Vol. 7. Date of Electronic Publication: 2018 Apr 25. - Publication Year :
- 2018
-
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 <superscript>b</superscript> , 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 <superscript>b</superscript> 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 <superscript>b</superscript> polymorphism is associated with increased odds of cerebral malaria. We also identify an apparent interaction between Sl2 and α <superscript>+</superscript> 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.<br />Competing Interests: DO, OS, AM, SU, GB, CN, EH, MT, AK, DD, OD, KL, CP, JM, MS, NM, NP, KM, AR, DK, KR, TW, JR No competing interests declared<br /> (© 2018, Opi et al.)
- Subjects :
- Adolescent
Case-Control Studies
Child
Child, Preschool
Female
Gene Frequency
Genetic Association Studies
Humans
Infant
Infant, Newborn
Kenya
Male
Mali
Models, Statistical
Malaria, Cerebral genetics
Malaria, Cerebral pathology
Polymorphism, Genetic
Receptors, Complement 3b genetics
alpha-Thalassemia genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 29690995
- Full Text :
- https://doi.org/10.7554/eLife.31579