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.

中文翻译：

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在乌干达的两个人口中，没有证据表明APOL1肾病风险等位基因与人类非洲锥虫病之间存在关联

背景

人类非洲锥虫病（HAT）表现为布鲁氏锥虫（Tbr）引起的急性形式，而布鲁氏冈比亚锥虫（Tbg）引起的慢性形式。先前的研究表明，宿主基因在感染结局中起着遗传作用，尤其是对于APOL1。我们已经在乌干达TBR和TBG HAT流行区开展的候选基因关联研究（CGA）的，以确定是否多态性IL10，IL8，IL4，HLAG，TNFA，TNX4LB，IL6，IFNG，MIF，APOL1，HLA-A ，IL1B，IL-4R，IL12B，IL12R，HP，HPR和CFH在HAT的作用。

方法和结果

我们分别包括了来自Busoga Tbr和西北乌干达Tbg流行地区的238和202名参与者。在CGAS中分析了单核苷酸多态性（SNP）基因型数据。这项研究的目的是发现比值比> 2，但是SNP与HAT的关联测试未产生正关联，即在多次测试校正后均无显着关联。但是，有强有力的证据表明，乌干达的Kabermaido地区与Tbr HAT和APOL1 G2的大小没有关系。

结论/意义

最近在乌干达中部的Soroti和Kaberamaido进行的一项研究发现，APOL1 G2等位基因与针对Tbr HAT的保护作用密切相关（优势比= 0.2，95％CI：0.07至0.48，p = 0.0001）。然而，在我们的研究中，尽管能够很好地找到类似大小的效应（OR = 0.9281，95％CI：0.482至1.788，p = 0.8035），但未发现G2对Tbr HAT的影响。G2等位基因在Soroti / Kabermaido病灶中可能受Tbr保护，但在种族和感染史不同的Busoga的Iganga区却不受Tbr保护。HAT感染结果和毒力的潜在机制很复杂，不同人群之间可能有所不同，并且可能涉及多个宿主，寄生虫甚至环境因素。