Candidate gene polymorphisms study between human African trypanosomiasis clinical phenotypes in Guinea



Kabore, Justin Windingoudi, Ilboudo, Hamidou, Noyes, Harry ORCID: 0000-0002-0656-200X, Camara, Oumou, Kabore, Jacques, Camara, Mamadou, Koffi, Mathurin, Lejon, Veerle, Jamonneau, Vincent, MacLeod, Annette
et al (show 6 more authors) (2017) Candidate gene polymorphisms study between human African trypanosomiasis clinical phenotypes in Guinea. PLOS NEGLECTED TROPICAL DISEASES, 11 (8). e0005833-.

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Abstract

<h4>Background</h4>Human African trypanosomiasis (HAT), a lethal disease induced by Trypanosoma brucei gambiense, has a range of clinical outcomes in its human host in West Africa: an acute form progressing rapidly to second stage, spontaneous self-cure and individuals able to regulate parasitaemia at very low levels, have all been reported from endemic foci. In order to test if this clinical diversity is influenced by host genetic determinants, the association between candidate gene polymorphisms and HAT outcome was investigated in populations from HAT active foci in Guinea.<h4>Methodology and results</h4>Samples were collected from 425 individuals; comprising of 232 HAT cases, 79 subjects with long lasting positive and specific serology but negative parasitology and 114 endemic controls. Genotypes of 28 SNPs in eight genes passed quality control and were used for an association analysis. IL6 rs1818879 allele A (p = 0.0001, OR = 0.39, CI95 = [0.24-0.63], BONF = 0.0034) was associated with a lower risk of progressing from latent infection to active disease. MIF rs36086171 allele G seemed to be associated with an increased risk (p = 0.0239, OR = 1.65, CI95 = [1.07-2.53], BONF = 0.6697) but did not remain significant after Bonferroni correction. Similarly MIF rs12483859 C allele seems be associated with latent infections (p = 0.0077, OR = 1.86, CI95 = [1.18-2.95], BONF = 0.2157). We confirmed earlier observations that APOL1 G2 allele (DEL) (p = 0.0011, OR = 2.70, CI95 = [1.49-4.91], BONF = 0.0301) is associated with a higher risk and APOL1 G1 polymorphism (p = 0.0005, OR = 0.45, CI95 = [0.29-0.70], BONF = 0.0129) with a lower risk of developing HAT. No associations were found with other candidate genes.<h4>Conclusion</h4>Our data show that host genes are involved in modulating Trypanosoma brucei gambiense infection outcome in infected individuals from Guinea with IL6 rs1818879 being associated with a lower risk of progressing to active HAT. These results enhance our understanding of host-parasite interactions and, ultimately, may lead to the development of new control tools.

Item Type: Article
Uncontrolled Keywords: TrypanoGEN Research Group as members of The H3Africa Consortium, Humans, Trypanosoma brucei gambiense, Trypanosomiasis, African, Genetic Predisposition to Disease, Phenotype, Polymorphism, Single Nucleotide, Guinea, Genetic Association Studies
Depositing User: Symplectic Admin
Date Deposited: 26 Feb 2018 07:35
Last Modified: 19 Jan 2023 06:39
DOI: 10.1371/journal.pntd.0005833
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3018384