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

Expert Rev Clin Immunol. 2022 Oct;18(10):1083-1090. doi: 10.1080/1744666X.2022.2117160. Epub 2022 Aug 30.

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; interferon-gamma; meta-analysis; multiple sclerosis; polymorphism; tumor necrosis factor-beta.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lymphotoxin-alpha / genetics*
  • Multiple Sclerosis* / genetics
  • Odds Ratio
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha