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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Abstract
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 |
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Status: | Published |
Refereed: | Yes |
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: | 2050-084X |
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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