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Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil.

巴西结核病病例接触者干扰素途径基因多态性与结核分枝杆菌感染风险。

  • 影响因子:2.89
  • DOI:10.1016/j.ijid.2019.12.013
  • 作者列表:"Cubillos-Angulo JM","Arriaga MB","Melo MGM","Silva EC","Alvarado-Arnez LE","de Almeida AS","Moraes MO","Moreira ASR","Lapa E Silva JR","Fukutani KF","Sterling TR","Hawn TR","Kritski AL","Oliveira MM","Andrade BB
  • 发表时间:2020-03-01
Abstract

BACKGROUND:Host genetic polymorphisms may be important in determining susceptibility to Mycobacterium tuberculosis (Mtb) infection, but their role is not fully understood. Detection of microbial DNA and activation of type I interferon (IFN) pathways regulate macrophage responses to Mtb infection. METHODS:We examined whether seven candidate gene SNPs were associated with tuberculin skin test (TST) positivity in close contacts of microbiologically confirmed pulmonary TB patients in Brazil. Independent associations with TST positivity were tested using multivariable logistic regression (using genotypes and clinical variables) and genetic models. RESULTS:Among 482 contacts of 145 TB index cases, 296 contacts were TST positive. Multivariable regression analysis adjusted for population admixture, age, family relatedness, sex and clinical variables related to increased TB risk demonstrated that SNPs in PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR]: 3.72; 95%CI=1.15-12.0; p=0.028) and in PYHIN1-IFI16-AIM2 rs1633256 (aOR=24.84; 95%CI=2.26-272.95; p=0.009) were associated with TST positivity in a recessive model. Furthermore, an IRF7 polymorphism (rs11246213) was associated with reduced odds of TST positivity in a dominant model (aOR: 0.50, 95%CI: 0.26-0.93; p=0.029). CONCLUSIONS:Polymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort.

摘要

背景: 宿主基因多态性在决定结核分枝杆菌 (Mtb) 感染易感性方面可能很重要,但其作用尚不完全清楚。微生物DNA的检测和I型干扰素 (IFN) 通路的激活调节巨噬细胞对Mtb感染的反应。 方法: 我们在巴西微生物学确诊的肺结核患者的密切接触者中检测了 7 个候选基因SNPs是否与结核菌素皮肤试验 (TST) 阳性相关。使用多变量logistic回归 (使用基因型和临床变量) 和遗传模型检测与TST阳性的独立相关性。 结果: 482 例TB指数病例的 145 名接触者中,296 名接触者TST阳性。多变量回归分析校正了与结核病风险增加相关的人群、年龄、家庭相关性、性别和临床变量,证明PYHIN1-IFI16-AIM2 的SNPs rs1101998 (校正OR [aOR]: 3.72; 95% CI = 1.15-12.0; p = 0.028) 和PYHIN1-IFI16-AIM2 rs1633256 (aOR = 24.84; 95% CI = 2.26-272.95; p = 0.009) 与隐性模型中TST阳性相关。此外,IRF7 多态性 (rs11246213) 与显性模型中TST阳性几率降低相关 (aOR: 0.50,95% CI: 0.26-0.93; p = 0.029)。 结论: 在巴西队列中,PYHIN1-IFI16-AIM2 rs1633256 、rs1101998 和IRF7 rs11246213 的多态性与Mtb感染易感性的改变相关。

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呼吸道感染方向

呼吸道感染分为上呼吸道感染与下呼吸道感染。上呼吸道感染是指自鼻腔至喉部之间的急性炎症的总称,是最常见的感染性疾病。下呼吸道感染是最常见的感染性疾患,治疗时必须明确引起感染的病原体以选择有效的抗生素。

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