No Association between TNF-α -308G/A Polymorphism and Idiopathic Recurrent Miscarriage: A Systematic Review with Meta-Analysis and Trial Sequential Analysis

BackgroundConflicting results were reported on the association between the TNF-α -308G/A polymorphism and idiopathic recurrent miscarriage (IRM). Though three meta-analyses have been conducted on this topic, the conclusions were contradictory, and the results may be unreliable as certain crucial conditions were neglected.MethodA complete search was conducted in PubMed, Cochrane Library, and Embase, other sources like Google Scholar, ClinicalTrial.gov and reference lists of relevant articles were also retrieved. All candidate articles were accessed and screened using specific inclusion and exclusion criteria. Statistical analyses were performed on data extracted from eligible studies using the STATA 12.0 software and the TSA 0.9 beta software.ResultsEventually, 12 case-control studies from 11 publications (with 1,807 cases and 2,012 controls) were included in this meta-analysis, and no evidence of any significant association was found in the overall analyses between the TNF-α -308G/A polymorphism and IRM risk. However, significant association was shown in Asian population (four studies from three publications) in the dominant model (AA + GA vs. GG), the allelic model (A vs. G), and the heterozygote model (GA vs. GG).ConclusionsTNF-α -308G/A polymorphism is not associated with IRM risk. Though significant association was found in Asian population, the result needs further confirmation from more studies.研究背景 既往关于肿瘤坏死因子-α（TNF-α）-308G/A多态性与特发性复发性流产（idiopathic recurrent miscarriage, IRM）的关联研究结果存在分歧。尽管已有3项针对该主题的荟萃分析，但所得结论相互矛盾，且由于忽略了某些关键条件，其结果可能并不可靠。 研究方法 本研究在PubMed、Cochrane图书馆、Embase数据库中开展了全面检索，同时还检索了Google Scholar、ClinicalTrials.gov等其他数据源以及相关文献的参考文献列表。所有候选文献均通过特定的纳入与排除标准进行筛选与评估。本研究采用STATA 12.0软件及TSA 0.9 beta软件，对符合纳入标准的研究所提取的数据进行统计学分析。 研究结果 本项荟萃分析最终纳入12项来自11篇文献的病例对照研究（case-control study），共包含1807例病例与2012例对照。整体分析结果显示，TNF-α-308G/A多态性与IRM发病风险无显著关联。但在亚洲人群亚组中（来自3篇文献的4项研究），显性遗传模型（AA + GA vs. GG）、等位基因模型（A vs. G）以及杂合子模型（GA vs. GG）均显示出显著关联。 研究结论 TNF-α-308G/A多态性与IRM发病风险并无关联。尽管在亚洲人群中观察到了显著关联，但该结果仍需更多研究进一步验证。