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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/25461 |
| _version_ | 1828168949794078720 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Anneli Cooper |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:43:15Z |
| format | Article |
| id | doaj.art-ab9c146982734133938529efb0976706 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:43:15Z |
| publishDate | 2017-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ab9c146982734133938529efb09767062022-12-22T03:51:16ZengeLife Sciences Publications LtdeLife2050-084X2017-05-01610.7554/eLife.25461APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasisAnneli Cooper0https://orcid.org/0000-0002-1159-142XHamidou Ilboudo1V Pius Alibu2Sophie Ravel3John Enyaru4William Weir5Harry Noyes6Paul Capewell7Mamadou Camara8Jacqueline Milet9Vincent Jamonneau10Oumou Camara11Enock Matovu12Bruno Bucheton13Annette MacLeod14https://orcid.org/0000-0002-0150-5049Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomCentre International de Recherche-Développement sur l'Elevage en zone Subhumide, Bobo-Dioulasso, Burkina Faso; TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, UgandaTrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda; College of Natural Sciences, Makerere University, Kampala, UgandaUnité Mixte de Recherche IRD-CIRAD 177, Institut de Recherche pour le Développement, Montpellier, FranceTrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda; College of Natural Sciences, Makerere University, Kampala, UgandaWellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomWellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda; Institute of Integrative Biology, University of Liverpool, Liverpool, United KingdomWellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomTrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda; Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Conakry, GuineaUnité Mixte de Recherche IRD-CIRAD 177, Institut de Recherche pour le Développement, Montpellier, FranceCentre 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, FranceProgramme National de Lutte contre la Trypanosomiase Humaine Africaine, Conakry, GuineaTrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda; College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, UgandaTrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda; Unité Mixte de Recherche IRD-CIRAD 177, Institut de Recherche pour le Développement, Montpellier, France; Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Conakry, GuineaWellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, UgandaReduced 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.https://elifesciences.org/articles/25461Trypanosoma bruceichronic kidney diseaseHuman African trypanosomiasissleeping sicknessTrypanosoma brucei gambienseTrypanosoma brucei rhodesiense |
| spellingShingle | 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 APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis eLife Trypanosoma brucei chronic kidney disease Human African trypanosomiasis sleeping sickness Trypanosoma brucei gambiense Trypanosoma brucei rhodesiense |
| title | APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis |
| title_full | APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis |
| title_fullStr | APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis |
| title_full_unstemmed | APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis |
| title_short | APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis |
| title_sort | apol1 renal risk variants have contrasting resistance and susceptibility associations with african trypanosomiasis |
| topic | Trypanosoma brucei chronic kidney disease Human African trypanosomiasis sleeping sickness Trypanosoma brucei gambiense Trypanosoma brucei rhodesiense |
| url | https://elifesciences.org/articles/25461 |
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