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

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 co...

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Autores principales: Cooper, Anneli, Ilboudo, Hamidou, Alibu, V Pius, Ravel, Sophie, Enyaru, John, Weir, William, Noyes, Harry, Capewell, Paul, Camara, Mamadou, Milet, Jacqueline, Jamonneau, Vincent, Camara, Oumou, Matovu, Enock, Bucheton, Bruno, MacLeod, Annette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495568/
https://www.ncbi.nlm.nih.gov/pubmed/28537557
http://dx.doi.org/10.7554/eLife.25461
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author Cooper, Anneli
Ilboudo, Hamidou
Alibu, V Pius
Ravel, Sophie
Enyaru, John
Weir, William
Noyes, Harry
Capewell, Paul
Camara, Mamadou
Milet, Jacqueline
Jamonneau, Vincent
Camara, Oumou
Matovu, Enock
Bucheton, Bruno
MacLeod, Annette
author_facet Cooper, Anneli
Ilboudo, Hamidou
Alibu, V Pius
Ravel, Sophie
Enyaru, John
Weir, William
Noyes, Harry
Capewell, Paul
Camara, Mamadou
Milet, Jacqueline
Jamonneau, Vincent
Camara, Oumou
Matovu, Enock
Bucheton, Bruno
MacLeod, Annette
author_sort Cooper, Anneli
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.25461.001
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spelling pubmed-54955682017-07-05 APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis Cooper, Anneli Ilboudo, Hamidou Alibu, V Pius Ravel, Sophie Enyaru, John Weir, William Noyes, Harry Capewell, Paul Camara, Mamadou Milet, Jacqueline Jamonneau, Vincent Camara, Oumou Matovu, Enock Bucheton, Bruno MacLeod, Annette eLife Genomics and Evolutionary Biology 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. DOI: http://dx.doi.org/10.7554/eLife.25461.001 eLife Sciences Publications, Ltd 2017-05-24 /pmc/articles/PMC5495568/ /pubmed/28537557 http://dx.doi.org/10.7554/eLife.25461 Text en © 2017, Cooper et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genomics and Evolutionary Biology
Cooper, Anneli
Ilboudo, Hamidou
Alibu, V Pius
Ravel, Sophie
Enyaru, John
Weir, William
Noyes, Harry
Capewell, Paul
Camara, Mamadou
Milet, Jacqueline
Jamonneau, Vincent
Camara, Oumou
Matovu, Enock
Bucheton, Bruno
MacLeod, Annette
APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis
title APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis
title_full APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis
title_fullStr APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis
title_full_unstemmed APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis
title_short APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis
title_sort apol1 renal risk variants have contrasting resistance and susceptibility associations with african trypanosomiasis
topic Genomics and Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495568/
https://www.ncbi.nlm.nih.gov/pubmed/28537557
http://dx.doi.org/10.7554/eLife.25461
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