Department of Respiratory and Critical Care Medicine, Chengdu First People's Hospital, Integrated TCM and Western Medicine Hospital Affiliated to Chengdu University of TCM, Chengdu City, Sichuan Province, 610000, China.
Department of Cardiology, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China.
Microb Pathog. 2021 Sep;158:104959. doi: 10.1016/j.micpath.2021.104959. Epub 2021 May 19.
Interleukin-4 (lL-4) is a critical negative cytokine in tuberculosis (TB) immune process, acting through modulating macrophages activation and Th1/Th2 balance. rs2243250 has been demonstrated to be associated with enhanced promoter strength in IL-4 expression. We performed a meta-analysis to assess the association between IL-4 rs2243250 polymorphism and TB risk.
We identified relevant studies by a comprehensive search of PubMed, Web of Science, and Embase databases, published up to February 10, 2021. The pooled odds ratios (ORs) and its 95% confidential intervals (95%CIs) were used to evaluate the associations under five genetic models. All statistical analyses were conducted with STATA 12.0 software.
Totally 11 qualified studies involving 3097 TB cases and 3697 controls were enrolled in this meta-analysis. Overall, we didn't detect any significant association between IL-4 rs2243250 polymorphism and TB risk (T vs. C: OR = 1.05, 95% CI = 0.85-1.30, p = 0; 65; TT + TC vs. CC: OR = 1.05, 95% CI = 0.73-1.50, p = 0.81; TT vs. TC + CC: OR = 1.10, 95% CI = 0.81-1.50, p = 0.54; TT vs. CC: OR = 1.17, 95% CI = 0.71-1.94, p = 0.54; TC vs. CC: OR = 1.03, 95% CI = 0.73-1.45, p = 0.88). Significant heterogeneity was identified in analyses under all genetic models. However, in the subgroup of European population, the recessive model provided an OR of 2.54 (1.30-4.96), with no significant between-study heterogeneity.
In conclusion, our meta-analysis indicated that IL-4 rs2243250 may increase TB risk in European population in recessive genetic model. Further research is needed to clarify the cause of ethnic difference in genetic association study.
白细胞介素-4（IL-4）是结核病（TB）免疫过程中的关键负细胞因子，通过调节巨噬细胞的激活和 Th1/Th2 平衡发挥作用。rs2243250 已被证明与 IL-4 表达的增强启动子强度相关。我们进行了一项荟萃分析，以评估 IL-4 rs2243250 多态性与 TB 风险之间的关联。
我们通过全面搜索 PubMed、Web of Science 和 Embase 数据库，确定了截至 2021 年 2 月 10 日发表的相关研究。使用五个遗传模型的汇总优势比（OR）及其 95%置信区间（95%CI）来评估关联。所有统计分析均使用 STATA 12.0 软件进行。
共有 11 项符合条件的研究纳入了这项荟萃分析，共纳入 3097 例 TB 病例和 3697 例对照。总体而言，我们没有发现 IL-4 rs2243250 多态性与 TB 风险之间存在任何显著关联（T 对 C：OR=1.05，95%CI=0.85-1.30，p=0.65；TT+TC 对 CC：OR=1.05，95%CI=0.73-1.50，p=0.81；TT 对 TC+CC：OR=1.10，95%CI=0.81-1.50，p=0.54；TT 对 CC：OR=1.17，95%CI=0.71-1.94，p=0.54；TC 对 CC：OR=1.03，95%CI=0.73-1.45，p=0.88）。在所有遗传模型的分析中均存在显著异质性。然而，在欧洲人群亚组中，隐性模型提供的 OR 为 2.54（1.30-4.96），无显著的研究间异质性。
总之，我们的荟萃分析表明，IL-4 rs2243250 可能会增加欧洲人群中 TB 的风险，尤其是在隐性遗传模型中。需要进一步的研究来阐明遗传关联研究中种族差异的原因。
