APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis

Cooper, A. et al. (2017) APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis. eLife, 6, e25461. (doi: 10.7554/eLife.25461) (PMID:28537557) (PMCID:PMC5495568)

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Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. In populations of African ancestry, two apolipoprotein-L1 (APOL1) variants with a recessive kidney disease risk, named G1 and G2, occur at high frequency. APOL1 is a trypanolytic protein that confers innate resistance to most African trypanosomes, but not Trypanosoma brucei rhodesiense or T.b. gambiense, which cause human African trypanosomiasis. In this case-control study we test the prevailing hypothesis that these APOL1 variants reduce trypanosomiasis susceptibility, resulting in their positive selection in sub-Saharan Africa. We demonstrate a five-fold dominant protective association for G2 against T.b. rhodesiense infection. Furthermore, we report unpredicted strong opposing associations with T.b. gambiense disease outcome. G2 associates with faster progression of T.b. gambiense trypanosomiasis, while G1 associates with asymptomatic carriage and undetectable parasitemia. These results implicate both forms of human African trypanosomiasis in the selection and persistence of otherwise detrimental APOL1 kidney disease variants.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Weir, Professor Willie and Alibu, Dr Vincent and MacLeod, Professor Annette and Capewell, Dr Paul and Matovu, Dr Enock and Cooper, Dr Anneli
Creator Roles:
Matovu, E.Conceptualization, Funding acquisition, Resources, Writing – review and editing
MacLeod, A.Conceptualization, Funding acquisition, Investigation, Writing – original draft, Writing – review and editing
Cooper, A.Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing
Weir, W.Formal analysis, Writing – review and editing
Alibu, V.Resources, Writing – review and editing
Capewell, P.Writing – original draft, Writing – review and editing
Authors: Cooper, A., Ilboudo, H., Alibu, V. P., Ravel, S., Enyaru, J., Weir, W., Noyes, H., Capewell, P., Camara, M., Milet, J., Jamonneau, V., Camara, O., Matovu, E., Bucheton, B., and MacLeod, A.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2017 Cooper et al.
First Published:First published in eLife 6:e25461
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
558214The origins and mechanisms of human infectivity in African trypanosomes.Annette MacLeodWellcome Trust (WELLCOTR)095201/Z/10/ZRI BIODIVERSITY ANIMAL HEALTH & COMPMED