Host genetics are important to consider in the role of resistance or susceptibility for developing active pulmonary tuberculosis (TB). Several association studies have reported the role of variants in STAT4 and TRAF1/C5 as risk factors to autoimmune diseases. Nevertheless, more data is needed to elucidate the role of these gene variants in infectious disease. Our data reports for the first time, variant rs10818488 in the TRAF1/C5 gene (found 47% of the population worldwide), is associated with susceptibility (OR = 1.51) to development TB. Multivariate analysis evidenced association between rs10818488 TRAF1/C5 and risk to multibacillary TB (OR = 4.18), confers increased bacteria load in the lung, indicates a decreased ability to control pathogen levels in the lung, and spread of the pathogen to new hosts. We showed that the “loss-of-function” variant in TRAF1/C5 led to susceptibility for TB by decreased production of TNF-α. Our results suggest the role of variant TRAF1/C5 in susceptibility to TB as well as in clinical presentation of multibacillary TB.

宿主遗传学对于发展活动性肺结核 (TB) 的耐药性或易感性的作用非常重要。一些关联研究报告了变异在STAT4和TRAF1/C5中的作用作为自身免疫性疾病的危险因素。然而，需要更多的数据来阐明这些基因变异在传染病中的作用。我们的数据首次报告，TRAF1/C5 基因中的变体 rs10818488（占全球人口的 47%）与发展为结核病的易感性（OR = 1.51）相关。多变量分析证明 rs10818488 TRAF1/C5 与多菌性结核病风险之间存在关联（OR = 4.18），导致肺部细菌负荷增加，表明控制肺部病原体水平的能力下降，以及病原体向新宿主的传播。我们发现 TRAF1/C5 中的“功能丧失”变体通过减少 TNF-α 的产生而导致对结核病的易感性。我们的结果表明变体TRAF1/C5的作用结核病的易感性以及多菌性结核病的临床表现。