Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.
;
Kirk Rockett ;
KatjaKivinen;
ChristinaHubbart;
Anna EJeffreys;
KateRowlands;
MuminatouJallow;
David J Conway ;
Kalifa A Bojang ;
MargaretPinder;
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StanleyUsen;
FatoumattaSisay-Joof;
GiorgioSirugo;
OusmaneToure;
Mahamadou A Thera ;
SalimataKonate;
SibirySissoko;
AmadouNiangaly;
BelcoPoudiougou;
Valentina DMangano;
Edith CBougouma;
Sodiomon BSirima;
DavidModiano;
Lucas NAmenga-Etego;
AnitaGhansah;
Kwadwo AKoram;
Michael DWilson;
AnthonyEnimil;
JenniferEvans;
Olukemi KAmodu;
SubuladeOlaniyan;
TobiasApinjoh;
ReginaMugri;
AndreNdi;
Carolyne MNdila;
SophieUyoga;
AlexanderMacharia;
NorbertPeshu;
Thomas NWilliams;
AlphaxardManjurano;
NunoSepúlveda;
Taane G Clark ;
EleanorRiley;
Chris Drakeley ;
HughReyburn;
VysaulNyirongo;
DavidKachala;
MalcolmMolyneux;
Sarah JDunstan;
Nguyen HoanPhu;
Nguyen NgocQuyen;
Cao QuangThai;
Tran TinhHien;
LaurensManning;
MosesLaman;
PeterSiba;
HarinKarunajeewa;
SteveAllen;
AngelaAllen;
Timothy MeDavis;
PascalMichon;
IvoMueller;
Síle FMolloy;
Susana Campino ;
AngelikiKerasidou;
Victoria JCornelius;
LeeHart;
Shivang SShah;
GavinBand;
Chris CaSpencer;
TsiriAgbenyega;
EricAchidi;
Ogobara KDoumbo;
JeremyFarrar;
KevinMarsh;
TerrieTaylor;
Dominic PKwiatkowski;
MalariaGEN Consortium;
(2017)
Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.
eLife, 6.
ISSN 2050-084X
DOI: 10.7554/eLife.15085
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.
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- Dept of Immunology and Infection (-2019)
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- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222559 (OA Location)
- 10.7554/eLife.15085 (DOI)
- 28067620 (PubMed)