Lack of association between TNFA and TNFB polymorphisms and the risk of multiple sclerosis: a meta-analysis from 37 studies

ABSTRACT

Background

Epidemiological studies about the association between genetic polymorphisms in TNFA, TNFB, and IFNG and the risk for multiple sclerosis (MS) have been performed extensively. However, the results are inconclusive. The purpose of this meta-analysis was to evaluate the contribution of the polymorphisms in TNFA, TNFB, and IFNG to the susceptibility of MS.

Methods

The PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched to identify relevant studies up to October 2021. A meta-analysis was performed, and pooled odds ratios (OR) and confidence intervals (CI) were computed using fixed or random effects models.

Results

A marginally significant association of the IFNG +874AT genotype with high risk of MS was observed in a heterozygous comparison (OR = 1.51, 95% CI, 1.02–2.23). However, no significant association between the TNFA (–308 G/A, – 238 G/A, and – 376 G/A) and TNFB +252A/G polymorphisms and MS risk was observed both in overall analysis and in subgroup analysis.

Conclusion

This meta-analysis provides evidence that the TNFA (–308 G/A, – 238 G/A, and – 376 G/A) and TNFB +252A/G polymorphisms were not risk factors for the occurrence of MS. Further studies with larger samples are necessary to reach the concise results about the contribution of other polymorphisms to the risk of MS.

KEYWORDS:

• Tumor necrosis factor-alpha
• tumor necrosis factor-beta
• meta-analysis
• interferon-gamma
• polymorphism
• multiple sclerosis

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer declares consulting and nonbranded speaker fees from Accordant, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, LabCorp, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, Viela Bio; and research support from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, NINDS, Novartis, Sanofi Genzyme. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

X Han and J Gu designed the study. J Gu and J Sun drafted the manuscript. X Han revised the manuscript. Y Zhang and X Wang collected the original data. J Sun performed statistical analysis. L Fu, L Li, D Wang, X Wang, and L Yu assisted in the performance of the statistical analysis. All authors agree for the final version of the manuscript to be published.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/1744666X.2022.2117160

Additional information

Funding

This work was supported by the Health Research Talents Project of Jilin Province [No.2019sc2018 and No. 20201SCI06], and Project of Development and Reform Commission of Jilin Province [No.2021C043-6].