Renal Risk Variants Have Contrasting Resistance and Susceptibility Associations with African Trypanosomiasis

Overview

Journal Elife

Specialty Biology

Date 2017 May 25

PMID 28537557

Citations 61

Authors

Anneli Cooper

Hamidou Ilboudo

V Pius Alibu

Sophie Ravel

John Enyaru

William Weir

Harry Noyes

Paul Capewell

Mamadou Camara

Jacqueline Milet

Vincent Jamonneau

Oumou Camara

Enock Matovu

Bruno Bucheton

Annette MacLeod

Affiliations

Soon will be listed here.

Abstract

Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. In populations of African ancestry, two ) 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 or which cause human African trypanosomiasis. In this case-control study, we test the prevailing hypothesis that these variants reduce trypanosomiasis susceptibility, resulting in their positive selection in sub-Saharan Africa. We demonstrate a five-fold dominant protective association for G2 against infection. Furthermore, we report unpredicted strong opposing associations with disease outcome. G2 associates with faster progression of 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 kidney disease variants.

Citing Articles

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