SNPs in IL4 and IFNG show no protective associations with human African trypanosomiasis in the Democratic Republic of the Congo: a case-control study

Asina, O. F., Noyes, H., Bucheton, B., MacLeod, A. , Ngoyi, D. M. and TrypanoGEN Group, (2021) SNPs in IL4 and IFNG show no protective associations with human African trypanosomiasis in the Democratic Republic of the Congo: a case-control study. AAS Open Research, 3, 35. (doi: 10.12688/aasopenres.12999.1) (PMID:32964195) (PMCID:PMC7481849)

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Abstract

Background: Human African trypanosomiasis (HAT) is a protozoal disease transmitted by tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self- cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, polymorphisms in 17 candidate genes were tested (APOL1 [G1 and G2], CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF, TNFA, IL6, IL4, IL8, IFNG, and HLA-G). Methods: Samples were collected in Democratic Republic of the Congo. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Commercial service providers genotyped polymorphisms at 96 single nucleotide polymorphisms (SNPs) on 17 genes. Data were analyzed using Plink V1.9 software and R. Loci, with suggestive associations (uncorrected p < 0.05) validated using an additional 594 individuals, including 164 cases and 430 controls. Results: After quality control, 87 SNPs remained in the analysis. Two SNPs in IL4 and two in IFNG were suggestively associated (uncorrected p<0.05) with a differential risk of developing a Trypanosoma brucei gambiense infection in the Congolese population. The IFNG minor allele (rs2430561, rs2069718) SNPs were protective in comparison between latent infections and controls. Carriers of the rs2243258_T and rs2243279_A alleles of IL4 and the rs2069728_T allele of IFNG had a reduced risk of developing illness or latent infection, respectively. None of these associations were significant after Bonferroni correction for multiple testing. A validation study using more samples was run to determine if the absence of significant association was due to lack of power. Conclusions: This study showed no evidence of an association of HAT with IL4 and IFNG SNPs or with APOL1 G1 and G2 alleles, which have been found to be protective in other studies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLeod, Professor Annette
Authors: Asina, O. F., Noyes, H., Bucheton, B., MacLeod, A., Ngoyi, D. M., and TrypanoGEN Group,
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:AAS Open Research
Publisher:F1000Research
ISSN:2515-9321
ISSN (Online):2515-9321
Copyright Holders:Copyright © 2020 Fataki Asina O et al.
First Published:First published in AAS Open Research 3:35
Publisher Policy:Reproduced under a Creative Commons licence

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