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Background <p>Pulmonary tuberculosis (PTB) is a chronic respiratory infectious disease with suboptimal treatment outcomes in some patients. The potential protective effect of aspirin against PTB and its underlying mechanisms remain unclear.</p> Methods <p>Two-sample Mendelian randomization (MR) was used to evaluate the association between aspirin use and PTB risk. Aspirin target genes from DrugBank were further assessed by summary-data-based Mendelian randomization (SMR) using eQTLGen and the Iceland dataset. Transcriptomic analysis compared gene expression between TB progressors and nonprogressors, and Kaplan–Meier analysis examined associations between gene expression and TB progression among household contacts. In vitro experiments were performed in BCG-stimulated monocytes.</p> Results <p>MR analysis showed that aspirin use was associated with reduced PTB risk (IVW: OR = 0.06, 95% CI: 0.01–0.51, <i>p</i> = 0.01). pQTL-based SMR identified significant associations of TNFAIP6 and NEU1 with PTB (<i>p</i> = 0.02, <i>p</i>-FDR = 0.03; <i>p</i> = 9.6 × 10⁻<sup>3</sup>, <i>p</i>-FDR = 0.03, respectively), whereas eQTL-based SMR showed no significant associations. Transcriptomic analysis revealed higher TNFAIP6 and NEU1 expression in progressors than in nonprogressors (<i>p</i> = 6.1 × 10⁻⁶ and <i>p</i> = 0.02). Kaplan–Meier analysis indicated that elevated TNFAIP6 and NEU1 expression was associated with increased TB progression risk among household contacts (<i>p</i> = 2.2 × 10⁻<sup>4</sup> and <i>p</i> = 0.03). In vitro, aspirin reduced TNFAIP6 expression in BCG-stimulated monocytes.</p> Conclusion <p>These findings suggest that aspirin may reduce PTB risk and implicate TNFAIP6 and NEU1 as potential mediators, supporting aspirin as a candidate adjunctive therapeutic strategy for PTB.</p>

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Integration of transcriptome and mendelian randomization elucidates the protective role of aspirin in pulmonary tuberculosis development

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Wei Tan,
  • Li Zhang,
  • Shanmei Wang,
  • Yu Chen,
  • Hanqing Yu,
  • Xinmiao Song,
  • Changwei Wu,
  • Ping Jiang,
  • Shuo Liang

摘要

Background

Pulmonary tuberculosis (PTB) is a chronic respiratory infectious disease with suboptimal treatment outcomes in some patients. The potential protective effect of aspirin against PTB and its underlying mechanisms remain unclear.

Methods

Two-sample Mendelian randomization (MR) was used to evaluate the association between aspirin use and PTB risk. Aspirin target genes from DrugBank were further assessed by summary-data-based Mendelian randomization (SMR) using eQTLGen and the Iceland dataset. Transcriptomic analysis compared gene expression between TB progressors and nonprogressors, and Kaplan–Meier analysis examined associations between gene expression and TB progression among household contacts. In vitro experiments were performed in BCG-stimulated monocytes.

Results

MR analysis showed that aspirin use was associated with reduced PTB risk (IVW: OR = 0.06, 95% CI: 0.01–0.51, p = 0.01). pQTL-based SMR identified significant associations of TNFAIP6 and NEU1 with PTB (p = 0.02, p-FDR = 0.03; p = 9.6 × 10⁻3, p-FDR = 0.03, respectively), whereas eQTL-based SMR showed no significant associations. Transcriptomic analysis revealed higher TNFAIP6 and NEU1 expression in progressors than in nonprogressors (p = 6.1 × 10⁻⁶ and p = 0.02). Kaplan–Meier analysis indicated that elevated TNFAIP6 and NEU1 expression was associated with increased TB progression risk among household contacts (p = 2.2 × 10⁻4 and p = 0.03). In vitro, aspirin reduced TNFAIP6 expression in BCG-stimulated monocytes.

Conclusion

These findings suggest that aspirin may reduce PTB risk and implicate TNFAIP6 and NEU1 as potential mediators, supporting aspirin as a candidate adjunctive therapeutic strategy for PTB.