Epstein-Barr virus-induced gene 3 (EBI3) polymorphisms and expression are associated with susceptibility to pulmonary tuberculosis
Epstein-Barr virus-induced gene 3 (EBI3) polymorphisms and expression are associated with susceptibility to pulmonary tuberculosis
复制标题
EB 病毒诱导基因 3 (EBI3) 多态性和表达与肺结核易感性相关。
DOI：
10.1016/j.tube.2015.03.009
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发表时间：
2015-07-01
期刊：
影响因子：
3.2
通讯作者：
Ge, Baoxue
中科院分区：
文献类型：
--
作者：
Zheng, Ruijuan;Liu, Haipeng;Ge, Baoxue
结核病（TB）仍然是一个主要的全球性健康问题，宿主遗传因素在结核病的易感性和耐药性中起着关键作用。本研究的目的是鉴定与结核病易感性相关的新的候选基因。我们进行了一项基于人群的病例对照研究，对跨越EB病毒诱导基因3（EBI 3）、集落刺激因子2（CSF 2）、IL-4、干扰素β 1（IFNB 1）、化因子（C-X-C基序）配体14（CXCL 14）和髓样分化初级应答基因88（Myd 88）中国435名肺结核患者和375名健康献血员的基因。我们观察到EBI 3基因rs 4740多态性与肺结核易感性相关，等位基因G与肺结核保护作用相关。此外，EBI 3缺陷导致感染牛分枝杆菌BCG的小鼠肺中的细菌负荷和组织病理学损伤减少。同时，在PTB患者的肉芽肿和BCG感染小鼠的肺组织中观察到较高丰度的EBI 3。值得注意的是，分枝杆菌感染在mRNA和蛋白水平上显著诱导巨噬细胞中EBI 3的表达。结论：EBI 3基因rs 4740多态性与结核病易感性密切相关，肺组织中EBI 3的升高和富集可能是结核病加重的原因之一，EBI 3至少部分来源于巨噬细胞。(C)2015爱思唯尔有限公司版权所有。
Tuberculosis (TB) remains a major global health problem and host genetic factors play a critical role in susceptibility and resistance to TB. The aim of this study was to identify novel candidate genes associated with TB susceptibility. We performed a population-based case-control study to genotype 13 tag SNPs spanning Epstein-Barr virus-induced gene 3 (EBI3), colony stimulating factor 2 (CSF2), IL-4, interferon beta 1 (IFNB1), chemokine (C-X-C motif) ligand 14 (CXCL14) and myeloid differentiation primary response gene 88 (Myd88) genes in 435 pulmonary TB patients and 375 health donors from China. We observed that EBI3 gene rs4740 polymorphism was associated with susceptibility to pulmonary tuberculosis (PTB) and the allele G was associated with a protective effect against PTB. Furthermore, EBI3 deficiency led to reduced bacterial burden and histopathological impairment in the lung of mice infected with Mycobacterium bovis BCG. Meanwhile, higher abundance of EBI3 was observed in the granuloma of PTB patients and in the lung tissue of BCG-infected mice. Of note, the expression of EBI3 in macrophages was remarkably induced by mycobacteria infection at both mRNA and protein level. In conclusion, EBI3 gene rs4740 polymorphism is closely associated with susceptibility to PTB and the elevation and enrichment of EBI3 in the lung which at least partially derived from macrophages may contribute to the exacerbation of mycobacterial infection. (C) 2015 Elsevier Ltd. All rights reserved.