Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controls

J Clin Periodontol. 2008 Sep;35(9):754-67. doi: 10.1111/j.1600-051X.2008.01298.x. Epub 2008 Jul 31.


Aim: We conducted a systematic review and a meta-analysis, in order to investigate the potential association of cytokine gene polymorphisms with either aggressive or chronic periodontal disease.

Material and methods: A comprehensive literature search was performed. We retrieved a total of 53 studies summarizing information about 4178 cases and 4590 controls. Six polymorphisms were included in our meta-analysis which are the following: IL-1A G[4845]T, IL-1A C[-889]T, IL-1B C[3953/4]T, IL-1B T[-511]C, IL-6 G[-174]C and TNFA G[-308]A. Random effect methods were used for the analysis. We calculated the specific odds ratios along with their 95% confidence intervals to compare the distribution of alleles and genotypes between cases and controls.

Results and conclusions: Using random effect methods we found statistically significant association of IL-1A C[-889]T and IL-1B C[3953/4]T polymorphisms with chronic periodontal disease without any evidence of publication bias or significant statistical heterogeneity. A weak positive association was also found concerning IL-1B T[-511]C and chronic periodontal disease. No association was found for all the cytokines examined as far as the aggressive form of the disease is concerned. Future studies may contribute to the investigation of the potential multigenetic predisposition of the disease and reinforce our findings.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adenine
  • Alleles
  • Chronic Periodontitis / genetics
  • Chronic Periodontitis / immunology
  • Cytosine
  • Genotype
  • Guanine
  • Humans
  • Interleukin-1alpha / genetics
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Interleukins / genetics*
  • Periodontitis / genetics
  • Periodontitis / immunology*
  • Polymorphism, Genetic / genetics*
  • Thymine
  • Tumor Necrosis Factor-alpha / genetics*


  • Interleukin-1alpha
  • Interleukin-1beta
  • Interleukin-6
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Guanine
  • Cytosine
  • Adenine
  • Thymine