The use of chronic gingivitis as reference status increases the power and odds of periodontitis genetic studies: a proposal based in the exposure concept and clearer resistance and susceptibility phenotypes definition

J Clin Periodontol. 2012 Apr;39(4):323-32. doi: 10.1111/j.1600-051X.2012.01859.x. Epub 2012 Feb 13.

Abstract

Aim: Current literature on chronic periodontitis genetics encompasses numerous single nucleotide polymorphisms-focused case-control studies with inconsistent and controversial results, which typically disregards the exposure concept embraced by case-control definition. Herein, we propose a case-control design reappraisal by clear phenotype selection, where chronic gingivitis represents a genetically resistant phenotype/genotype opposing the susceptible cohort.

Material and methods: The hypothesis was tested in healthy, chronic periodontitis and gingivitis groups through Real-time PCR-based allelic discrimination of classic variants IL1B-3954, IL6-174, TNFA-308, IL10-592 and TLR4-299.

Results: Observed allele/genotype frequencies characterize the healthy group with an intermediate genetic profile between periodontitis and gingivitis cohorts. When comparing genotype/allele frequencies in periodontitis versus healthy and periodontitis versus gingivitis scenarios, the number of positive associations (2-4) and the degree of association (p and odds ratio values) were significantly increased by the new approach proposed (periodontitis versus gingivitis), suggesting the association of IL1B-3954, TNFA-308, IL10-592 and TLR4-299 with periodontitis risk. Power study was also significantly improved by the new study design proposed when compared to the traditional approach.

Conclusions: The data presented herein support the use of new case-control study design based on the case-control definition and clear resistance/susceptibility phenotypes selection, which can significantly impact the study power and odds of identification of genetic factors involved in PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Chronic Disease
  • Chronic Periodontitis / genetics*
  • Female
  • Gene Frequency
  • Genes, Dominant
  • Genes, Recessive
  • Genetic Predisposition to Disease
  • Gingivitis / genetics*
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Male
  • Middle Aged
  • Models, Genetic*
  • Multivariate Analysis
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Reference Values
  • Research Design
  • Toll-Like Receptor 4 / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-1beta
  • Interleukin-6
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Interleukin-10