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 ORCID: 0000-0002-0656-200X, Capewell, Paul, Camara, Mamadou, Milet, Jacqueline
et al (show 5 more authors) (2017) APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis. ELIFE, 6. e25461-.

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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: Article
Uncontrolled Keywords: Humans, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosomiasis, African, Kidney Diseases, Genetic Predisposition to Disease, Case-Control Studies, Genotype, Alleles, Africa South of the Sahara, Selection, Genetic, Disease Resistance, Apolipoprotein L1
Depositing User: Symplectic Admin
Date Deposited: 06 Feb 2019 10:45
Last Modified: 19 Jan 2023 01:05
DOI: 10.7554/eLife.25461
Open Access URL: https://doi.org/10.7554/eLife.25461
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3032360