title: Interleukin-6 polymorphisms are associated with pathogenic bacteria in subjects with periodontitis.
abstract: BACKGROUND
  Growing evidence suggests that individual genetic susceptibility may influence the host's response to infections. Previously, we showed that a common variation in the interleukin (IL)-6 gene was associated with increased odds of detection of common periodontal pathogens from individuals with aggressive periodontitis. The aim of this study was to investigate the association between IL-6 polymorphisms and periodontopathogenic bacteria in a larger, ethnically mixed population of subjects with periodontitis.
  
  
  METHODS
  Genomic DNA was extracted from 107 subjects diagnosed with severe forms of periodontitis to study a cluster of polymorphisms in inflammatory genes, including IL-6. The presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Tannerella forsythia (previously T. forsythensis) in their subgingival biofilm was determined by polymerase chain reaction analysis. Serum IL-6 and C-reactive protein (CRP) concentrations were analyzed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Multiple logistic regression analysis revealed that the IL-6 -6106 polymorphism was associated with the detection of A. actinomycetemcomitans (P = 0.009; odds ratio [OR] = 3.5; 95% confidence interval [CI]: 1.38 to 9.16) and the concomitant detection of A. actinomycetemcomitans and P. gingivalis (P = 0.015; OR = 3.6; 95% CI: 1.28 to 10.04). The IL-6 -174 polymorphism was associated with increased odds of the concomitant detection of A. actinomycetemcomitans and P. gingivalis (P = 0.042; OR = 2.8; 95% CI: 1.04 to 7.75). Haplotype analysis of all five IL-6 polymorphisms confirmed an association with the detection of A. actinomycetemcomitans (P = 0.046). The IL-6 -6106 polymorphism was also associated with CRP serum levels at multivariate analysis (P = 0.024).
  
  
  CONCLUSIONS
  These findings confirm the hypothesis that complex interactions between the microbiota and host genome are at the basis of susceptibility to periodontitis. Periodontal disease may represent a useful model to study the pathways and mechanisms of host-pathogen interactions in inflammatory diseases.
authors.affiliation: Eastman Dental Hospital, University College London, London, UK. l.nibali@eastman.ucl.ac.uk
authors.forename: Luigi
authors.initials: L
authors.lastname: Nibali
authors.forename: Maurizio S
authors.initials: MS
authors.lastname: Tonetti
authors.forename: Derren
authors.initials: D
authors.lastname: Ready
authors.forename: Mohamed
authors.initials: M
authors.lastname: Parkar
authors.forename: Peter M
authors.initials: PM
authors.lastname: Brett
authors.forename: Nikos
authors.initials: N
authors.lastname: Donos
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Aiuto
mesh_terms: D000328:Adult; D000368:Aged; D016976:Aggregatibacter actinomycetemcomitans / Q000254:growth & development*; D001439:Bacteroides / Q000254:growth & development*; D018441:Biofilms; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010518:Periodontitis / Q000276:immunology* / Q000382:microbiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D016966:Porphyromonas gingivalis / Q000254:growth & development*; D012907:Smoking
chemical_list: D015850:Interleukin-6; D002097:C-Reactive Protein