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Genetic variation in human HBB is associated with Plasmodium falciparum transmission

Abstract

Genetic factors are known to have a role in determining susceptibility to infectious diseases1,2, although it is unclear whether they may also influence host efficiency in transmitting pathogens. We examine variants in HBB that have been shown to be protective against malaria3 and test whether these are associated with the transmission of the parasite from the human host to the Anopheles vector. We conducted cross-sectional malariological surveys on 3,739 human subjects and transmission experiments involving 60 children and 6,446 mosquitoes in Burkina Faso, West Africa. Protective hemoglobins C (HbC, β6Glu→Lys)4,5 and S (β6Glu→Val)6,7,8 are associated with a twofold in vivo (odds ratio 2.17, 95% CI 1.57–3.01, P = 1.0 × 10−6) and a fourfold ex vivo (odds ratio 4.12, 95% CI 1.90–9.29, P = 7.0 × 10−5) increase of parasite transmission from the human host to the Anopheles vector. This provides an example of how host genetic variation may influence the transmission dynamics of an infectious disease.

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Figure 1: Plasmodium falciparum gametocyte rate according to hemoglobin C homozygosis in children living in rural villages of Burkina Faso, West Africa.

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Acknowledgements

We are grateful to the study participants for their understanding and cooperation and to the laboratory and field staff of the IRSS/Centre Muraz of Bobo Dioulasso and of the Centre Medical Saint Camille of Ouagadougou, Burkina Faso, for skilled work, logistics and collaboration. We are indebted to the staff of the IRD Antenne de Bobo Dioulasso for logistic support. We thank G. Modiano, V. Petrarca, B. Arcà and M. Coluzzi for continuous advice and L. Ranford-Cartwright and E. Ferraro for statistical support. This work was funded by grants from the EU, Sixth Framework Programme, BioMalPar Network of Excellence, LSHP-CT-2004-503578 and from the Istituto Pasteur–Fondazione Cenci Bolognetti, University of Rome 'La Sapienza'.

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L.C.G. organized and supervised the parasitological and entomological surveys in the Bobo Dioulasso area. G.B. performed parasitological, entomological and genetic surveys in the Bobo Dioulasso area. F.Y. and B.Y. participated in parasitological, entomological and genetic surveys. K.R.D. participated to entomological surveys. J.S. organized and performed the parasitological and genetic survey in the Ouagadougou area. J.B.O. coordinated the study in the Bobo Dioulasso area. D.M. proposed the scientific hypothesis and organized and coordinated the study. L.C.G., C.C., J.B.O. and D.M. designed the research procedure. L.C.G., G.B., J.B.O. and D.M. analyzed and interpreted the data. D.M. and L.C.G. wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to David Modiano.

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The authors declare no competing financial interests.

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Gouagna, L., Bancone, G., Yao, F. et al. Genetic variation in human HBB is associated with Plasmodium falciparum transmission. Nat Genet 42, 328–331 (2010). https://doi.org/10.1038/ng.554

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