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.
Highlights
Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease caused by infection with extracellular blood protozoan parasites, which are transmitted by the bite of the tsetse fly (Glossina sp) (Headrick, 2014).The disease is present in more than 250 foci in Africa and nearly 70 million people are at risk of infection with the two human-infective forms
This study showed no evidence of an association of HAT with IL4 and IFNG single nucleotide polymorphisms (SNPs) or with APOL1 G1 and G2 alleles, which have been found to be protective in other studies
We found suggestive associations with HAT at SNP loci in IL4, IFNG, IL6 and MIF, but none of these remained significant after a Bonferroni correction
Summary
Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease caused by infection with extracellular blood protozoan parasites, which are transmitted by the bite of the tsetse fly (Glossina sp) (Headrick, 2014).The disease is present in more than 250 foci in Africa and nearly 70 million people are at risk of infection with the two human-infective forms. Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease caused by infection with extracellular blood protozoan parasites, which are transmitted by the bite of the tsetse fly (Glossina sp) (Headrick, 2014). About 97% of all HAT cases are due to Tbg infection, which causes a chronic disease with a long latency period (Kennedy, 2013). The control of Tbg HAT is mainly based on the active detection of infected cases followed by their treatment and vector control. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Two SNPs in IL4 and two in IFNG were suggestively associated (uncorrected p
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