Tian Haokun, Guan Zhen, Li Shen, Wang Jianhua
Laboratory of Translational Medicine, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Neurol. 2024 Jul 16;15:1411184. doi: 10.3389/fneur.2024.1411184. eCollection 2024.
Our study aimed to assess the association between gene 3' untranslated region insertion/deletion (3'UTR I/D) and A55V (alanine/valine) polymorphisms and neural tube defects (NTDs) susceptibility.
According to pre-determined inclusion and exclusion criteria, the article search was conducted to search articles published before October 2023. Two authors independently screened the included articles and extracted their basic characteristics. After quality evaluation, the meta-analysis and trial sequential analysis (TSA) were conducted using RevMan 5.4, Stata/MP 17, and TSA 0.9.5.10 Beta. Subgroup analysis was conducted based on country and case group composition. Sensitivity analysis was conducted using a one-by-one exclusion method. Begg's and Egger's tests were used to evaluate publication bias.
A total of seven articles were included. Overall meta-analysis revealed significant heterogeneity among the included studies for 3'UTR I/D polymorphism of the gene. Significant statistical data indicated that those with the DD genotype and D allele had higher chances of NTD compared to those with the II genotype and the I allele, respectively. The combined result of II vs. ID was not statistically significant. A55V variation showed no statistical significance in the risk of NTD, despite the absence of significant heterogeneity across the included studies. Most of the heterogeneity was resolved after subgrouping, and a higher risk of the ID genotype was found than the II genotype for Chinese people. Genotyping NTD patients or their mothers was not a factor affecting the heterogeneity. Sensitivity analysis and publication bias analysis suggested that positive findings supported our results.
The gene 3'UTR I/D polymorphism increased the likelihood of developing NTDs in the Chinese population, with the D allele being the risk factor, which contributed to the understanding of the genetic basis of NTDs. TSA indicated that more high-quality original studies were needed in the future for further validation.
本研究旨在评估基因3'非翻译区插入/缺失（3'UTR I/D）和A55V（丙氨酸/缬氨酸）多态性与神经管缺陷（NTDs）易感性之间的关联。
根据预先确定的纳入和排除标准，检索2023年10月之前发表的文章。两位作者独立筛选纳入的文章并提取其基本特征。经过质量评估后，使用RevMan 5.4、Stata/MP 17和TSA 0.9.5.10 Beta进行荟萃分析和试验序贯分析（TSA）。基于国家和病例组构成进行亚组分析。采用逐一排除法进行敏感性分析。使用Begg检验和Egger检验评估发表偏倚。
共纳入7篇文章。总体荟萃分析显示，纳入研究中基因3'UTR I/D多态性存在显著异质性。显著的统计数据表明，与II基因型和I等位基因的人相比，DD基因型和D等位基因的人患NTD的几率更高。II与ID的合并结果无统计学意义。尽管纳入研究之间不存在显著异质性，但A55V变异在NTD风险中无统计学意义。亚组分析后大部分异质性得到解决，发现中国人中ID基因型的风险高于II基因型。对NTD患者或其母亲进行基因分型不是影响异质性的因素。敏感性分析和发表偏倚分析表明，阳性结果支持我们的结果。
基因3'UTR I/D多态性增加了中国人群患NTDs的可能性，D等位基因为危险因素，这有助于理解NTDs的遗传基础。TSA表明，未来需要更多高质量的原始研究进行进一步验证。
