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Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α + thalassaemia.

Authors :
Opi DH
Swann O
Macharia A
Uyoga S
Band G
Ndila CM
Harrison EM
Thera MA
Kone AK
Diallo DA
Doumbo OK
Lyke KE
Plowe CV
Moulds JM
Shebbe M
Mturi N
Peshu N
Maitland K
Raza A
Kwiatkowski DP
Rockett KA
Williams TN
Rowe JA
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.)

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