Ahouty Bernardin, Koffi Mathurin, Ilboudo Hamidou, Simo Gustave, Matovu Enock, Mulindwa Julius, Hertz-Fowler Christiane, Bucheton Bruno, Sidibé Issa, Jamonneau Vincent, MacLeod Annette, Noyes Harry, N'Guetta Simon-Pierre
Laboratoire de Génétique, Félix Houphouët Boigny University, Abidjan, Côte d'Ivoire.
Unité de Recherche en Génétique et Epidémiology Moléculaire, Jean Lorougnon Guédé University, Daloa, Côte d'Ivoire.
PLoS Negl Trop Dis. 2017 Oct 23;11(10):e0005992. doi: 10.1371/journal.pntd.0005992. eCollection 2017 Oct.
Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions. A candidate gene association study was conducted in Côte d'Ivoire using a case-control design which included a total of 233 subjects (100 active HAT cases, 100 controls and 33 latent infections). All three possible pairwise comparisons between the three phenotypes were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77 SNPs passed quality control. There were suggestive associations at three loci in IL6 and TNFA in the comparison between active cases and controls, one SNP in each of APOL1, MIF and IL6 in the comparison between latent infections and active cases and seven SNP in IL4, HLA-G and TNFA between latent infections and controls. No associations remained significant after Bonferroni correction, but the Benjamini Hochberg false discovery rate test indicated that there were strong probabilities that at least some of the associations were genuine. The excess of associations with latent infections despite the small number of samples available suggests that these subjects form a distinct genetic cluster different from active HAT cases and controls, although no clustering by phenotype was observed by principle component analysis. This underlines the complexity of the interactions existing between host genetic polymorphisms and parasite diversity.
人类非洲锥虫病（HAT）即昏睡病，是一种被忽视的热带病。长期以来，它一直被视为一种必然致命的疾病，但越来越多的证据表明，布氏冈比亚锥虫感染可导致多种临床结果，包括潜伏感染，即通过显微镜检查无法检测到寄生虫的长期感染。这种临床多样性的决定因素尚不清楚，但可能部分归因于多个基因中的寄生虫或宿主遗传多样性，或它们之间的相互作用。在科特迪瓦进行了一项候选基因关联研究，采用病例对照设计，共纳入233名受试者（100例活动性HAT病例、100名对照和33例潜伏感染）。使用16个候选基因（IL1、IL4、IL4R、IL6、IL8、IL10、IL12、IL12R、TNFA、INFG、MIF、APOL1、HPR、CFH、HLA - A和HLA - G）中的96个单核苷酸多态性（SNP）对三种表型之间的所有三种可能的成对比较进行了测试。77个SNP的数据通过了质量控制。在活动性病例与对照的比较中，IL6和TNFA的三个位点存在提示性关联；在潜伏感染与活动性病例的比较中，APOL1、MIF和IL6各有一个SNP存在关联；在潜伏感染与对照之间，IL4、HLA - G和TNFA有七个SNP存在关联。经Bonferroni校正后，没有关联仍然显著，但Benjamini Hochberg错误发现率检验表明，至少一些关联很可能是真实的。尽管可用样本数量较少，但与潜伏感染的关联过多，这表明这些受试者形成了一个与活动性HAT病例和对照不同的独特遗传簇，尽管主成分分析未观察到按表型聚类。这突出了宿主基因多态性与寄生虫多样性之间存在的相互作用的复杂性。
