-308 G > A of TNF-α gene promoter decreases the risk of multiple sclerosis: a meta-analysis

Mult Scler. 2011 Jun;17(6):658-65. doi: 10.1177/1352458510394009. Epub 2010 Dec 22.

Abstract

Background: Environmental and genetic factors are thought to be involved in the pathogenesis of multiple sclerosis (MS). Polymorphisms of tumor necrosis factor (TNF)-α -308 were implicated in MS risk in several case-control association studies. However, the studies have shown inconsistent results.

Objectives: To address the association of G/A polymorphisms of TNF-α -308 with MS risk by meta-analysis.

Methods: Thirteen studies were included. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated.

Results: A total of 1870 cases and 2769 controls were included in the meta-analysis. The pooled result indicated that -308 A allele is significantly associated with reduced risk of MS compared with -308 G allele (A vs. G, p=0.022). The same pattern of the result was also obtained in the contrasts of AA+ GA vs. GG (p=0.008) and GA vs. GG (p=0.007). For AA vs. GG or AA vs. GA + GG, no significant association was detected most likely caused by very low frequency or non-availability of homozygote genotype AA for all of the studies.

Conclusions: TNF-α -308 A allele is associated with reduced risk of MS.

Publication types

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

MeSH terms

  • Case-Control Studies
  • Chi-Square Distribution
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Linear Models
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / prevention & control
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Risk Assessment
  • Risk Factors
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Tumor Necrosis Factor-alpha