No evidence for association between APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations

Kimuda, M. P. et al. (2018) No evidence for association between APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations. PLoS Neglected Tropical Diseases, 12(2), e0006300. (doi: 10.1371/journal.pntd.0006300) (PMID:29470556) (PMCID:PMC5844566)

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Background: Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT. Methodology and results: We included 238 and 202 participants from the Busoga Tbr and Northwest Uganda Tbg endemic areas respectively. Single Nucleotide Polymorphism (SNP) genotype data were analysed in the CGAS. The study was powered to find odds ratios > 2 but association testing of the SNPs with HAT yielded no positive associations i.e. none significant after correction for multiple testing. However there was strong evidence for no association with Tbr HAT and APOL1 G2 of the size previously reported in the Kabermaido district of Uganda. Conclusions/Significance: A recent study in the Soroti and Kaberamaido focus in Central Uganda found that the APOL1 G2 allele was strongly associated with protection against Tbr HAT (odds ratio = 0.2, 95% CI: 0.07 to 0.48, p = 0.0001). However, in our study no effect of G2 on Tbr HAT was found, despite being well powered to find a similar sized effect (OR = 0.9281, 95% CI: 0.482 to 1.788, p = 0.8035). It is possible that the G2 allele is protective from Tbr in the Soroti/Kabermaido focus but not in the Iganga district of Busoga, which differ in ethnicity and infection history. Mechanisms underlying HAT infection outcome and virulence are complex and might differ between populations, and likely involve several host, parasite or even environmental factors.

Item Type:Articles
Additional Information:This study was funded by the Wellcome Trust under the H3Africa initiative as Grant number 099310/Z/12/Z.
Glasgow Author(s) Enlighten ID:MacLeod, Professor Annette
Creator Roles:
MacLeod, A.Funding acquisition, Writing – review and editing
Authors: Kimuda, M. P., Noyes, H., Mulindwa, J., Enyaru, J., Alibu, V. P., Sidibe, I., Mumba Ngoyi, D., Hertz-Fowler, C., MacLeod, A., Tastan Bishop, Ö., and Matovu, E.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2018 Kimuda et al.
First Published:First published in PLoS Neglected Tropical Diseases 12(2):e0006300
Publisher Policy:Reproduced under a Creative Commons License

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