ASSOCIATION OF Fcγ RECEPTOR IIa (CD32) POLYMORPHISM WITH SEVERE MALARIA IN WEST AFRICA

GRAHAM S. COOKE Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Medical Research Council Laboratories, Banjul, The Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom

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CHRISTOPHE AUCAN Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Medical Research Council Laboratories, Banjul, The Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom

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ANDREW J. WALLEY Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Medical Research Council Laboratories, Banjul, The Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom

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SHELLEY SEGAL Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Medical Research Council Laboratories, Banjul, The Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom

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BRIAN M. GREENWOOD Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Medical Research Council Laboratories, Banjul, The Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom

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DOMINIC P. KWIATKOWSKI Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Medical Research Council Laboratories, Banjul, The Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom

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ADRIAN V. S. HILL Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Medical Research Council Laboratories, Banjul, The Gambia; London School of Hygiene and Tropical Medicine, London, United Kingdom

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Malaria continues to claim the lives of more children worldwide than any other infectious disease, and improved understanding of disease immunology is a priority for the development of new therapeutic and vaccination strategies. FcγRIIa (CD32) contains a polymorphic variant (H/R131) that has been associated with variability in susceptibility to both bacterial diseases and Plasmodium falciparum parasitemia. We investigated the role of this polymorphism in West Africans with mild and severe malarial disease. The HH131 genotype was significantly associated with susceptibility to severe malaria (P = 0.03, odds ratio = 1.40, 95% confidence interval = 1.02–1.91). In contrast to studies of parasitemia, the presence of the R131 allele, rather than the RR131 genotype, appeared to be the important factor in protection from disease. This is the first evidence for an association between CD32 polymorphism and severe malaria and provides an example of balancing selective pressures from different infectious diseases operating at the same genetic locus.

Author Notes

Reprint requests: Graham S. Cooke, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom, E-mail: grahamc@well.ox.ac.uk.
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