AUTHOR=Tian Haokun , Guan Zhen , Li Shen , Wang Jianhua TITLE=Association between UCP2 gene 3’UTR I/D and A55V polymorphisms and neural tube defects susceptibility: systematic review, meta-analysis, and trial sequential analysis JOURNAL=Frontiers in Neurology VOLUME=Volume 15 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1411184 DOI=10.3389/fneur.2024.1411184 ISSN=1664-2295 ABSTRACT=Aim: Our study aimed to access the association between UCP2 gene 3'UTR insertion/deletion (I/D) and A55V (alanine/valine) polymorphisms and neural tube defects (NTDs) susceptibility. Materials and methods: According to pre-determined inclusion and exclusion criteria, the article searching 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 were conducted using RevMan 5.4, StataMP 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. Results: A total of 7 articles were included. Overall meta-analysis revealed significant heterogeneity among the included studies for 3' untranslated region insertion/deletion (3'UTR I/D) polymorphism of UCP2 gene. Significant statistical data indicated that those with DD genotype and D allele had higher chances of NTD compared to those with II genotype and I allele, respectively. The combined result of the 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 higher risk of ID genotype was found than II genotype for Chinese people. Genotyping NTDs patients or their mothers were not the factor affecting the heterogeneity. Sensitivity analysis and publication bias analysis suggested positive findings supported our results. Conclusion: The UCP2 gene 3'UTR I/D polymorphism increased the likelihood of developing NTDs in the Chinese population, with D allele being the risk factor, which contributed to the understanding of the genetic basis of NTDs. Trial sequential analysis indicated that more high-quality original studies were needed in the future for further validation.