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

eLife

John Enyaru¹  Paul Capewell¹  Oumou Camara²  Annette MacLeod³  V Pius Alibu⁴  Vincent Jamonneau⁴  Hamidou Ilboudo⁵  Sophie Ravel⁶  Harry Noyes⁶  Bruno Bucheton⁶  William Weir⁷  Anneli Cooper⁸  Jacqueline Milet⁸  Mamadou Camara⁸  Enock Matovu⁸ 

[1] College of Natural Sciences, Makerere University, Kampala, Uganda;Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom;Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Conakry, Guinea;TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda;Centre International de Recherche-Développement sur l'Elevage en zone Subhumide, Bobo-Dioulasso, Burkina Faso;TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda;Unité Mixte de Recherche IRD-CIRAD 177, Institut de Recherche pour le Développement, Montpellier, France;Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;

关键词: Trypanosoma brucei;    chronic kidney disease;    Human African trypanosomiasis;    sleeping sickness;    Trypanosoma brucei gambiense;    Trypanosoma brucei rhodesiense;   

DOI  :  10.7554/eLife.25461

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown