Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research On Tropical Diseases, National Institute of Parasitic Diseases, Shanghai 200025, China; School of Global Health, Chinese Center for Tropical Diseases Research-Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Infect Genet Evol. 2023 Dec;116:105524. doi: 10.1016/j.meegid.2023.105524. Epub 2023 Nov 11.
Numerous observational studies have previously reported an association between inflammatory cytokines and tuberculosis (TB). However, the causal relationship between these factors remains unclear. Consequently, we conducted two-sample Mendelian randomization (MR) analyses to ascertain the causal link between levels of inflammatory cytokines and the risk of TB.
Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene. SNP was obtained from genome-wide association studies (GWAS) of 8293 individuals of Finnish. TB data was obtained from the UK Biobank, which included 46,293 individuals of European ancestry (comprising 2277 TB cases and 46,056 controls). Two-sample, bi-directional MR analyses using inverse-variance weighted (IVW) method as the primary analysis. Followed by comprehensive sensitivity analyses to validate the robustness of results.
The study showed that the causal relationship between circulating levels of interleukin (IL)-7 and risk of TB (odds ratio [OR] = 1.001, 95% confidence intervals [CIs]: 1.000, 1.003. p = 0.047). No causal associations were observed between other influencing factors and the occurrence of TB. Furthermore, the analysis revealed that TB infection exhibited negative causal associations with macrophage inflammatory protein 1 alpha ([MIP-1α], OR = 0.007, 95% CI: 0.000, 0.192. p = 0.004), IL-2 (OR = 0.014, 95% CI: 0.010, 0.427. p = 0.014), interleukin-2 receptor alpha chain([IL-2rα], OR = 0.019, 95% CI: 0.001, 0.525. p = 0.019) and basic fibroblast growth factor ([bFGF], OR = 0.066, 95% CI: 0.006, 0.700. p = 0.024).
The study has illuminated the causal link between inflammatory cytokines and TB, thereby enhancing our comprehension of the potential mechanisms underlying TB pathogenesis. This discovery offers promising avenues for the identification of novel therapeutic targets in TB treatment. These insights may ultimately pave the way for more effective treatment approaches, thereby improving patient outcomes.
先前有大量观察性研究报告称，炎症细胞因子与结核病（TB）之间存在关联。然而，这些因素之间的因果关系尚不清楚。因此，我们进行了两样本孟德尔随机化（MR）分析，以确定炎症细胞因子水平与 TB 风险之间的因果关系。
单核苷酸多态性（SNP）与细胞因子密切相关，位于其编码基因内或附近。SNP 来自于芬兰 8293 名个体的全基因组关联研究（GWAS）。TB 数据来自 UK Biobank，其中包括 46293 名欧洲血统个体（包括 2277 例 TB 病例和 46056 名对照）。使用逆方差加权（IVW）法作为主要分析方法进行两样本双向 MR 分析。随后进行全面的敏感性分析以验证结果的稳健性。
研究表明，循环白细胞介素（IL）-7 水平与 TB 风险之间存在因果关系（比值比[OR] = 1.001，95%置信区间[CI]：1.000，1.003，p = 0.047）。没有观察到其他影响因素与 TB 发生之间存在因果关系。此外，分析表明，TB 感染与巨噬细胞炎症蛋白 1 阿尔法（[MIP-1α]，OR = 0.007，95%CI：0.000，0.192，p = 0.004）、IL-2（OR = 0.014，95%CI：0.010，0.427，p = 0.014）、白细胞介素-2 受体 alpha 链（[IL-2rα]，OR = 0.019，95%CI：0.001，0.525，p = 0.019）和碱性成纤维细胞生长因子（[bFGF]，OR = 0.066，95%CI：0.006，0.700，p = 0.024）之间存在负向因果关系。
该研究阐明了炎症细胞因子与 TB 之间的因果关系，从而增强了我们对 TB 发病机制潜在机制的理解。这一发现为 TB 治疗中新型治疗靶点的确定提供了有希望的途径。这些见解最终可能为更有效的治疗方法铺平道路，从而改善患者的预后。
