A Meta-Analysis of the Association between the CC Chemokine Ligand 5 (CCL5) -403 G>A Gene Polymorphism and Tuberculosis Susceptibility

AimMany case-control studies have been performed in the recent past to investigate the association between CCL5 -403 G>A (rs2107538) gene polymorphism and tuberculosis (TB) susceptibility in various ethnic groups. However, these studies have produced inconsistent and contradictory results. In the present study, meta-analysis was performed to assess the association between CCL5 -403 G>A polymorphism and TB risk.MethodologyQuantitative synthesis was done for the published studies based upon association between CCL5 -403 G>A polymorphism and TB risk from PubMed (Medline), EMBASE web search. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models.ResultsA total of six studies comprising 1638 confirmed TB cases and 1519 healthy controls were included in this meta-analysis. Variant A allele (A vs. G: p = 0.035; OR = 1.301, 95% CI = 1.019 to 1.662) and variant homozygous (AA vs. GG; p = 0.001; OR = 1.520, 95% CI = 1.202 to 1.923) carriers were significantly associated with TB susceptibility. Similarly, recessive model (AA vs. GG+GA: p = 0.016; OR = 1.791, 95% CI = 1.117 to 2.873) also indicated increased TB risk. Whereas, heterozygous (GA vs. GG: p = 0.837; OR = 1.028, 95% CI = 0.791 to 1.335) and dominant (AA+GA vs. GG: p = 0.222; OR = 1.188, 95% CI = 0.901 to 1.567) models failed to show increased risk of developing TB.ConclusionsThis meta-analysis suggests that there is a significant association between the CCL5 -403 G>A polymorphism and increased risk of TB. However, larger well-designed epidemiological studies with stratified case control and biological characterization may be helpful to validate this association.研究目的：既往已有多项病例对照研究，旨在探讨不同种族人群中CCL5基因-403 G>A（rs2107538）多态性与结核病（TB）易感性的关联，但此类研究所得结果并不一致，甚至相互矛盾。本研究通过荟萃分析（meta-analysis），评估CCL5 -403 G>A多态性与结核病患病风险的关联。 研究方法：通过PubMed（Medline）、EMBASE数据库检索已发表的关于CCL5 -403 G>A多态性与结核病患病风险关联的研究，并进行定量综合分析。针对等位基因对比、纯合子、杂合子、显性及隐性五种遗传模型，计算合并比值比（OR）及95%置信区间（95%CI）。 结果：本荟萃分析共纳入6项研究，包含1638例确诊结核病患者与1519名健康对照个体。变异型A等位基因（A vs. G：p=0.035；OR=1.301，95%CI=1.019~1.662）与变异型纯合子（AA vs. GG：p=0.001；OR=1.520，95%CI=1.202~1.923）携带者均与结核病易感性存在显著关联。同样，隐性遗传模型（AA vs. GG+GA：p=0.016；OR=1.791，95%CI=1.117~2.873）也提示结核病患病风险升高。而杂合子模型（GA vs. GG：p=0.837；OR=1.028，95%CI=0.791~1.335）与显性遗传模型（AA+GA vs. GG：p=0.222；OR=1.188，95%CI=0.901~1.567）未显示结核病患病风险升高。 结论：本荟萃分析表明，CCL5 -403 G>A多态性与结核病患病风险升高存在显著关联。但仍需开展更大样本量、设计严谨的分层病例对照流行病学研究，并结合生物学特征验证该关联。