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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.

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