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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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Detalles Bibliográficos
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
Descripción
Sumario: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