Interleukin-10 Promoter Gene Polymorphisms and Susceptibility to Tuberculosis: A Meta-Analysis

ObjectiveAs an update to other recent meta-analyses, the purpose of this study was to explore whether interleukin-10 (IL-10) polymorphisms and their haplotypes contribute to tuberculosis (TB) susceptibility.MethodsWe searched for published case-control studies examining IL-10 polymorphisms and TB in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wanfang databases and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strengths of the associations.ResultsA total of 28 studies comprising 8,242 TB patients and 9,666 controls were included in the present study. There were no significant associations between the -1082G/A, -819C/T, and -592A/C polymorphisms and TB in the pooled samples. Subgroup analyses revealed that the -819T allele was associated with an increased TB risk in Asians in all genetic models (T vs. C: OR=1.17, 95% CI=1.05-1.29, P=0.003; TT vs. CC: OR=1.37, 95% CI=1.09-1.72, P=0.006; CT+TT vs. CC: OR=1.33, 95% CI=1.09-1.63, P=0.006; TT vs. CT+CC: OR=1.17, 95% CI=1.02-1.35, P=0.03) and that the -592A/C polymorphism was significantly associated with TB in Europeans under two genetic models (A vs. C: OR=0.77, 95% CI=0.60-0.98, P=0.03; AA vs. CC: OR=0.53, 95% CI=0.30-0.95, P=0.03). Furthermore, the GCC IL-10 promoter haplotype was associated with an increased risk of TB (GCC vs. others: P=1.42, 95% CI=1.02-1.97, P=0.04). Subgroup analyses based on ethnicity revealed that the GCC haplotype was associated with a higher risk of TB in Europeans, whereas the ACC haplotype was associated with a lower TB risk in both Asians and Europeans.ConclusionsThis meta-analysis suggests that the IL-10-819T/C polymorphism is associated with the risk of TB in Asians and that the IL-10-592A/C polymorphism may be a risk factor for TB in Europeans. Furthermore, these data indicate that IL-10 promoter haplotypes play a vital role in the susceptibility to or protection against the development of TB.研究目的：作为近期其他荟萃分析的更新研究，本研究旨在探讨白细胞介素10（IL-10）基因多态性及其单倍型是否与结核病（TB）易感性相关。研究方法：我们在PubMed、EMBASE、考克兰对照试验中心注册库（CENTRAL）、万方数据库（Wanfang databases）以及中国知网（CNKI）中检索已发表的、探讨IL-10基因多态性与TB关联的病例对照研究。采用比值比（OR）及95%置信区间（CI）评估二者关联的强度。研究结果：本研究最终纳入28项相关研究，共包含8242名结核病患者与9666名对照个体。合并样本分析显示，-1082G/A、-819C/T及-592A/C基因多态性与TB发病风险无显著关联。亚组分析结果表明，在所有遗传模型下，-819T等位基因与亚洲人群的TB发病风险升高相关（T vs. C：OR=1.17，95%CI=1.05~1.29，P=0.003；TT vs. CC：OR=1.37，95%CI=1.09~1.72，P=0.006；CT+TT vs. CC：OR=1.33，95%CI=1.09~1.63，P=0.006；TT vs. CT+CC：OR=1.17，95%CI=1.02~1.35，P=0.03）；而在两种遗传模型下，-592A/C基因多态性与欧洲人群的TB发病风险显著相关（A vs. C：OR=0.77，95%CI=0.60~0.98，P=0.03；AA vs. CC：OR=0.53，95%CI=0.30~0.95，P=0.03）。此外，IL-10启动子区GCC单倍型与TB发病风险升高相关（GCC vs. 其他单倍型：OR=1.42，95%CI=1.02~1.97，P=0.04）。基于种族的亚组分析显示，GCC单倍型与欧洲人群的TB发病风险升高相关，而ACC单倍型则在亚洲人群与欧洲人群中均与TB发病风险降低相关。结论：本荟萃分析结果提示，IL-10-819T/C基因多态性与亚洲人群的TB发病风险相关，而IL-10-592A/C基因多态性可能是欧洲人群TB发病的风险因素。此外，本研究数据表明IL-10启动子区单倍型在结核病的易感性或防护中发挥重要作用。