TNFA gene polymorphisms and the risk of endometriosis: An updated meta-analysis of genetic association studies

Abstract

The tumor necrosis factor-alpha (TNFA) gene plays a pivotal role in modulating inflammatory responses, and its variants have been hypothesized to influence susceptibility to endometriosis, a complex and multifactorial gynecological condition. Among the notable polymorphisms investigated are -238 G>A, -308 G>A, -850 C>T, -857 C>T, -863 C>A, and -1031 T>C. Despite substantial research, the evidence regarding their role as genetic risk factors for endometriosis remains inconclusive. To address this uncertainty, the present study conducted a systematic review of the literature to evaluate the association between TNFA variants and endometriosis risk. A comprehensive search of electronic databases was performed to identify relevant studies. Data extraction and quality assessment were carried out using the Newcastle-Ottawa Scale. Pooled odds ratios and 95% confidence intervals were calculated across various genetic models, with adjustments for multiple comparisons using the Bonferroni correction. Trial sequential analysis (TSA) was employed to determine the required sample size for conclusive results, and Egger’s test was used to assess publication bias. The analysis included 18 studies examining different TNFA polymorphisms, but no significant associations with endometriosis risk were identified. TSA revealed that the existing sample sizes were inadequate to detect definitive links. While the findings suggest that upstream variants of the TNFA gene are not associated with endometriosis risk, this does not conclusively rule out a role for TNFA in the disease pathogenesis. Further research involving larger, ethnically diverse populations is warranted to confirm these results and provide deeper insights into the genetic factors contributing to endometriosis.

Keywords

Endometriosis / Tumor necrosis factor-alpha / Endometriosis / Gene polymorphism

Acknowledgments

None.

Funding

None.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author contributions

Conceptualization: Amrit Sudershan, Parvinder Kumar

Investigation: Amrit Sudershan, Showkat Ahmad Malik, Srishty, Feroze Ahmed Dar, Bashir Ahmad Sheikh, Mehraj Bashir

Methodology: Amrit Sudershan, Srishty Sudershan, Agar Chander Pushap, Mohd Anis Ganaie, Irfan Ahmad Bhat, Mohd Younis, Parvinder Kumar, Showkat Ahmad Malik, Mehraj Bashir

Formal analysis: Amrit Sudershan, Irfan Ahmad Bhat, Showkat Ahmad Najar, Mohd Younis

Writing - original draft: Amrit Sudershan, Agar Chander Pushap, Srishty Sudershan

Writing - review & editing: Showkat Ahmad Malik, Srishty Sudershan, Agar Chander Pushap, Mohd Anis Ganaie, Bashir Ahmad Sheikh, Mehraj Bashir

All authors collaborated on finalizing the manuscript and provided valuable feedback throughout the process, ultimately endorsing the final version.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

All the data analyzed in the present study were downloaded from online databases such as PubMed and Web of Science.

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