Ofon Elvis, Noyes Harry, Mulindwa Julius, Ilboudo Hamidou, Simuunza Martin, Ebo'o Vincent, Njiokou Flobert, Koffi Mathurin, Bucheton Bruno, Fogue Pythagore, Hertz-Fowler Christiane, MacLeod Annette, Simo Gustave
Molecular Parasitology & Entomology Unit, Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
Centre for Genomic Research, University of Liverpool, Liverpool, United Kingdom.
PLoS Negl Trop Dis. 2017 Oct 27;11(10):e0005979. doi: 10.1371/journal.pntd.0005979. eCollection 2017 Oct.
Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH).
A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test.
Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204-0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness.
The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP.
人类非洲锥虫病（HAT）是一种被忽视的疾病，目标是到2020年将其作为公共卫生问题予以消除。要实现消除目标，需要更好地了解HAT的流行病学和临床演变情况。除了HAT的经典临床演变外，在西非还报告了无症状携带者和自发治愈的情况。有人提出人类对HAT易感性存在遗传因素，以解释这些新观察到的感染反应。为了测试与感染反应的遗传关联，对17个基因（APOL1、IL1B、IL4、IL4R、IL6、IL8、IL12B、IL12RB1、IL10、TNFA、INFG、MIF、HLA - G、HLA - A、HP、HPR和CFH）中的基因多态性进行了检测。
对从喀麦隆收集的180份血液样本进行了病例对照研究，其中包括56例病例和124例对照。从血液样本中提取DNA。经过质量控制后，排除了25个样本（24例对照和1例病例）。对包括55例病例和100例对照的155名个体进行基因分型，检测位于17个基因上的96个位点（88个单核苷酸多态性和8个插入缺失）。通过病例对照关联试验评估这些位点与HAT之间的关联。
对所选基因中鉴定出的96个位点中的64个单核苷酸多态性和4个插入缺失进行分析发现，触珠蛋白（HP）中rs8062041的次要等位基因（T）似乎对HAT具有保护作用（p = 0.0002395，比值比0.359（95%可信区间[0.204 - 0.6319]））；表明病例中的频率高于对照。这个校正后p值为0.0163的次要等位基因与患昏睡病的较低风险（保护作用）相关。
触珠蛋白相关蛋白HPR和HP紧密连锁，在一些人中两者都有重复，可能导致活性更高。尽管该单核苷酸多态性位于HP内，但这种产量增加可能是与rs8062041相关的保护作用的原因。
