Abstract：
BACKGROUND: Several epidemiological studies have suggested that genetic variations in encoding pattern recognition receptors (PRRs) genes such as Toll Like Receptors (TLRs) and their signaling products, may influence the susceptibility, severity and outcome of tuberculosis (TB). After sensing a pathogen, the cell responds producing an inflammatory response, to restrain the pathogen\'s successful course of infection. Herein we assessed single nucleotide polymorphisms (SNP) and gene expression from pathogen recognition and inflammasome pathways in Brazilian TB patients.
RESULTS: For genetic association analysis we included MYD88 and TLR4, PRRs sensing proteins. Allele distribution for MYD88 rs6853 (A > G) and TLR4 rs7873784 (C > G) presented conserved among the tested samples with statistically differential distribution in TB patients versus controls. However, when testing according to sample ethnicity (African or Caucasian-derived individuals) we identified that the rs6853 G/G genotype was associated with a lower susceptibility to TB in Caucasian population. Meanwhile, the rs7873784 G/G genotype was associated with a higher TB susceptibility in Afro-descendant ethnicity individuals. We also aimed to verify MYD88 and the inflammasome genes NLRP1 and NLRC4 expression in order to connect to active TB and/or clinical aspects.
CONCLUSIONS: We identified that inflammasome gene expression in TB patients under treatment display a similar pattern as in healthy controls, indicating that TB treatment impairs NLRP1 inflammasome activation.
RESULTS: For genetic association analysis we included MYD88 and TLR4, PRRs sensing proteins. Allele distribution for MYD88 rs6853 (A > G) and TLR4 rs7873784 (C > G) presented conserved among the tested samples with statistically differential distribution in TB patients versus controls. However, when testing according to sample ethnicity (African or Caucasian-derived individuals) we identified that the rs6853 G/G genotype was associated with a lower susceptibility to TB in Caucasian population. Meanwhile, the rs7873784 G/G genotype was associated with a higher TB susceptibility in Afro-descendant ethnicity individuals. We also aimed to verify MYD88 and the inflammasome genes NLRP1 and NLRC4 expression in order to connect to active TB and/or clinical aspects.
CONCLUSIONS: We identified that inflammasome gene expression in TB patients under treatment display a similar pattern as in healthy controls, indicating that TB treatment impairs NLRP1 inflammasome activation.
摘要：
背景：一些流行病学研究表明，编码模式识别受体（PRR）基因如Toll样受体（TLR）及其信号传导产物的遗传变异，可能会影响易感性，结核病（TB）的严重程度和结果。在感应到病原体后，细胞产生炎症反应，以抑制病原体的成功感染过程。在此，我们评估了巴西结核病患者中来自病原体识别和炎症体途径的单核苷酸多态性（SNP）和基因表达。
结果：对于遗传关联分析，我们包括MYD88和TLR4，PRRs传感蛋白。MYD88rs6853（A>G）和TLR4rs7873784（C>G）的等位基因分布在测试样品中保守，在TB患者与对照组中具有统计学差异分布。然而,在根据样本种族(非洲或白种人来源的个体)进行检测时,我们发现rs6853G/G基因型与白种人人群对TB的易感性较低相关.同时,rs7873784G/G基因型与非洲裔种族个体中更高的TB易感性相关.我们还旨在验证MYD88和炎症体基因NLRP1和NLRC4的表达，以便与活动性结核病和/或临床方面联系起来。
结论：我们发现，在接受治疗的结核病患者中，炎性体基因表达与健康对照相似。表明结核病治疗损害NLRP1炎性体激活。
结果：对于遗传关联分析，我们包括MYD88和TLR4，PRRs传感蛋白。MYD88rs6853（A>G）和TLR4rs7873784（C>G）的等位基因分布在测试样品中保守，在TB患者与对照组中具有统计学差异分布。然而,在根据样本种族(非洲或白种人来源的个体)进行检测时,我们发现rs6853G/G基因型与白种人人群对TB的易感性较低相关.同时,rs7873784G/G基因型与非洲裔种族个体中更高的TB易感性相关.我们还旨在验证MYD88和炎症体基因NLRP1和NLRC4的表达，以便与活动性结核病和/或临床方面联系起来。
结论：我们发现，在接受治疗的结核病患者中，炎性体基因表达与健康对照相似。表明结核病治疗损害NLRP1炎性体激活。
