The association between tumor necrosis factor alpha promoter polymorphisms and ankylosing spondylitis: a meta-analysis

Hum Immunol. 2013 Oct;74(10):1357-62. doi: 10.1016/j.humimm.2013.06.037. Epub 2013 Jul 2.

Abstract

Background: Studies investigating the association between tumor necrosis factor (TNF)-alpha promoter polymorphisms and ankylosing spondylitis have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship.

Methods: We performed a systematic search of the National Library of Medline and Embase databases before January 2013. This meta-analysis included 14 case-control studies, which included 1607 ankylosing spondylitis cases and 1910 controls.

Results: The combined results based on all studies showed that ankylosing spondylitis cases had a significantly lower frequency of -308GA [OR (codominant model)=0.81, 95% CI=0.66, 0.99, P=0.04], -857CT [OR (codominant model)=0.55, 95% CI=0.32, 0.94, P=0.03], -863AA [OR (codominant model)=0.11, 95% CI=0.01, 0.94, P=0.04], -863CA [OR (codominant model)=0.32, 95% CI=0.18, 0.58, P<0.001], and -1031TC [OR (codominant model)=0.44, 95% CI=0.25, 0.77, P=0.004] genotype. However, ankylosing spondylitis cases had a significantly higher frequency of -238AA [OR (recessive model)=7.43, 95% CI=3.66, 15.05, P<0.001] and -850TT [OR (recessive model)=2.49, 95% CI=1.16, 5.34, P=0.02; OR (codominant model)=2.83, 95% CI=1.28, 6.25, P=0.01] genotype. In the subgroup analysis by race, we found that ankylosing spondylitis cases had a significantly higher frequency of -238AA [OR (recessive model)=7.43, 95% CI=3.66, 15.05, P<0.001] genotype in Caucasians and lower frequency of -857CT [OR (codominant model)=0.53, 95% CI=0.30, 0.94, P=0.03] in Asians.

Conclusions: Our meta-analysis suggests that TNF-alpha promoter polymorphisms at positions -238, -308, -850, -857, -863 and -1031 could have a small influence on ankylosing spondylitis susceptibility. But there is a lack of association of the TNF-alpha-376G/A and -646G/A polymorphisms with ankylosing spondylitis.

Publication types

  • Meta-Analysis

MeSH terms

  • Alleles
  • Case-Control Studies
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Publication Bias
  • Spondylitis, Ankylosing / genetics*
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • TNF protein, human
  • Tumor Necrosis Factor-alpha