Association between TNF-α polymorphisms and gestational diabetes mellitus: a meta-analysis and trial sequential...

Area of Science:

• Genetics and Molecular Biology
• Reproductive Health
• Immunology

Background:

• Conflicting evidence exists regarding the association between tumor necrosis factor-α (TNF-α) gene polymorphisms and gestational diabetes mellitus (GDM) risk.
• Specific polymorphisms, including rs1800629, rs361525, and rs1799724, have been implicated but require further investigation.

Purpose of the Study:

• To conduct a comprehensive meta-analysis to clarify the relationship between TNF-α gene polymorphisms (rs1800629, rs361525, rs1799724) and GDM susceptibility.
• To provide conclusive evidence by pooling data from multiple studies.

Main Methods:

• A systematic literature search was performed across major databases (PubMed, Embase, CNKI, Wanfang).
• Eligible studies were analyzed using meta-analysis, calculating odds ratios (ORs) and 95% confidence intervals (CIs) across five genetic models.
• Subgroup analyses and trial sequential analysis (TSA) were employed to assess the robustness of findings.

Main Results:

• The meta-analysis included 15 studies with 1289 GDM cases and 1445 controls.
• A significant association was identified between TNF-α rs1800629 polymorphism and increased GDM risk, particularly in the Asian subgroup (e.g., allele model: p=0.001, OR=2.20).
• No significant association was found between TNF-α rs361525 or rs1799724 polymorphisms and GDM risk across all genetic models.

Conclusions:

• The TNF-α rs1800629 polymorphism is confirmed as a risk factor for GDM in Asian populations.
• No association was observed between TNF-α rs361525/rs1799724 and GDM risk.
• Further multi-ethnic studies with larger sample sizes are recommended to validate these null associations.