Promoter variants of tumor necrosis factor-alpha (G-308 a: rs1800629 and C-857 T:rs1799724) are linked to type 1 diabetes: A meta-analysis and trial sequential analysis

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI:10.1016/j.cyto.2025.157082

Shengnan Zhang, Zhenyu Li, Xiaodong Yang

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引用次数: 0

Abstract

Introduction

Tumor necrosis factor-alpha (TNF-α) is associated with type 1 diabetes through complex immunological and metabolic pathways, highlighting its multifaceted role. Genetic differences, particularly in the TNF-α gene promoter region, influence individual susceptibility to type 1 diabetes by altering gene expression. Numerous studies have examined the link between TNF-α polymorphisms and type 1 diabetes in various populations, yielding inconsistent results. This research explores the relationship between TNF-α and type 1 diabetes through a detailed meta-analysis of existing studies.

Materials and methods

This meta-analysis examined four SNPs in the TNF-α gene promoter region: G-238 A, G-308 A, C-587 T, and T-1031C. Literature searches were conducted using PubMed, ScienceDirect, Google Scholar, Embase, Web of Science, and Scopus. Relevant articles were systematically reviewed, and qualifying studies were selected based on specific inclusion and exclusion criteria. The analysis was performed using Comprehensive Meta-Analysis software, version 4.

Results

Twenty-four case-control studies were suitable for examining the link between TNF-α polymorphisms and T1D susceptibility. Genetic comparison models showed an association between the TNF-α G-308 A and C-857 T variants and T1D risk, and sensitivity analysis confirmed these findings. Trial sequential analysis further validated the genetic relationship between TNF-α promoter variants (G-308 A and C-857 T) and indicated that sufficient studies were available for a conclusive meta-analysis. Conversely, no significant association was found between the promoter polymorphisms G-238 A and T-1031C and T1D onset, and TSA suggested the need for further research across diverse populations.

Conclusions

Variations in the TNF-α promoter at positions G-308 A and C-857 T are linked to an increased risk of T1D.

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肿瘤坏死因子α启动子变异（G-308 a: rs1800629和C-857 T:rs1799724）与1型糖尿病有关：一项荟萃分析和试验序列分析

肿瘤坏死因子-α (TNF-α)通过复杂的免疫和代谢途径与1型糖尿病相关，突出了其多方面的作用。遗传差异，特别是在TNF-α基因启动子区域，通过改变基因表达影响个体对1型糖尿病的易感性。许多研究已经在不同人群中检测了TNF-α多态性与1型糖尿病之间的联系，但结果不一致。本研究通过对现有研究的详细荟萃分析，探讨了TNF-α与1型糖尿病之间的关系。材料和方法本荟萃分析检测了TNF-α基因启动子区域的四个snp: G-238 A， G-308 A， C-587 T和T- 1031c。文献检索使用PubMed、ScienceDirect、b谷歌Scholar、Embase、Web of Science和Scopus进行。系统地回顾相关文献，并根据特定的纳入和排除标准选择符合条件的研究。分析使用综合元分析软件，版本4。结果24项病例对照研究适合探讨TNF-α多态性与T1D易感性之间的关系。遗传比较模型显示TNF-α G-308 A和C-857 T变异与T1D风险之间存在关联，敏感性分析证实了这些发现。试验序列分析进一步验证了TNF-α启动子变异（G-308 A和C-857 T）之间的遗传关系，并表明有足够的研究可用于结论性荟萃分析。相反，没有发现启动子多态性G-238 A和T-1031C与T1D发病有显著关联，TSA提示需要在不同人群中进一步研究。结论TNF-α启动子g - 308a和c - 857t位点的变异与T1D风险增加有关。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.