<i>APOL1</i> 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) <i>APOL1</i> renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis. ELIFE, 6. e25461-.

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Abstract

Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. In populations of African ancestry, two <i>apolipoprotein-L1 (APOL1</i>) 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 <i>Trypanosoma brucei rhodesiense</i> or <i>T.b. gambiense,</i> which cause human African trypanosomiasis. In this case-control study, we test the prevailing hypothesis that these <i>APOL1</i> variants reduce trypanosomiasis susceptibility, resulting in their positive selection in sub-Saharan Africa. We demonstrate a five-fold dominant protective association for G2 against <i>T.b. rhodesiense</i> infection. Furthermore, we report unpredicted strong opposing associations with <i>T.b. gambiense</i> disease outcome. G2 associates with faster progression of <i>T.b. gambiense</i> 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 <i>APOL1</i> 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: 30 Jan 2024 10:39
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
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