A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations,PLOS Neglected Tropical Diseases

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A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations
PLOS Neglected Tropical Diseases ( IF 3.4 ) Pub Date : 2017-10-27 , DOI: 10.1371/journal.pntd.0005979
Elvis Ofon ₁ , Harry Noyes ₂ , Julius Mulindwa ₃ , Hamidou Ilboudo ₄ , Martin Simuunza ₅ , Vincent Ebo'o ₆ , Flobert Njiokou ₇ , Mathurin Koffi ₈ , Bruno Bucheton _{9,

10} , Pythagore Fogue ₁ , Christiane Hertz-Fowler ₂ , Annette MacLeod ₁₁ , Gustave Simo ₁ ,

Affiliation

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.
Department of Biochemistry, CONAS, Makerere University, Kampala, Uganda.
Unité de recherche sur les bases biologiques de la lutte intégrée, Centre International de Recherche-Développement sur l'Elevage en zone Subhumide (CIRDES), Bobo-Dioulasso, Burkina Faso.
Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka, Zambia.
National Sleeping sickness control Program of Cameroon, Ministry of Public Health, Yaoundé, Cameroon.
Laboratory of Molecular Biology, Department of Animal Biology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon.
Laboratoire des interactions Hôte-Microorganismes-Environnement et Evolution, Unité de Formation et de Recherche Environnement, Université Jean Lorougnon Guédé, Daloa, Côte d'Ivoire.
Institut de Recherche pour le Développement (IRD), UMR INTERTRYP IRD-CIRAD, Campus international de Baillarguet, Montpellier, France.
Programme National de Lutte contre la Trypanosomose Humaine Africaine, Conakry, Guinea.
Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Garscube Estate, Glasgow, United Kingdom.

Background

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).

Methodology

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.

Results

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.

Conclusion

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.

中文翻译：

触珠蛋白的多态性，触珠蛋白相关蛋白基因座与喀麦隆人群中人类昏睡病的风险有关

背景

人类非洲锥虫病 (HAT) 是一种被忽视的疾病，目标是到 2020 年作为公共卫生问题消除。消除需要更好地了解 HAT 的流行病学和临床演变。除了 HAT 的经典临床演变之外，西非还报告了无症状携带者和自发治愈。有人提出人类对 HAT 易感性的遗传成分可以解释这些新观察到的对感染的反应。为了测试与感染反应的遗传关联，测试了 17 个基因的遗传多态性（APOL1、IL1B、IL4、IL4R、IL6、IL8、IL12B、IL12RB1、IL10、TNFA、INFG、MIF、HLA-G、HLA-A、HP、HPR 和 CFH )。

方法

对来自喀麦隆的 56 名病例和 124 名对照者的 180 份血液样本进行了病例对照研究。从血液样本中提取 DNA。质控后剔除样本25个（对照24个，病例1个）。在位于 17 个基因上的 96 个位点（88 个 SNP 和 8 个插入缺失）对 155 个个体（包括 55 个病例和 100 个对照）进行了基因分型。这些基因座和 HAT 之间的关联是通过病例对照关联测试估计的。

结果

对选定基因中鉴定的 96 个 SNP 和 4 个插入缺失的分析表明，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, OR 0.359 (CI ₉₅ [0.204–0.6319) ])); 表明与对照组相比，病例的频率更高。这种调整后p值为 0.0163 的次要等位基因与发生昏睡病的风险（保护作用）较低有关。