Association of interleukin-1 gene polymorphisms with early-onset periodontitis

J Clin Periodontol. 2000 Sep;27(9):682-9. doi: 10.1034/j.1600-051x.2000.027009682.x.

Abstract

Background, aims: Early-onset periodontal diseases (EOP) are a group of inflammatory disorders characterised by a rapid rate of periodontal tissue destruction, in young individuals who are otherwise healthy. There is now substantial evidence to suggest that genetic factors play a rôle in the pathogenesis of EOP but the precise nature of these factors remains unclear. Polymorphisms in cytokine genes which may underpin inter-individual differences in cytokine synthesis and secretion have been associated with other diseases which have an inflammatory pathogenesis, including chronic adult periodontal disease (CAPD).

Method: We therefore investigated the frequency of polymorphisms in the genes encoding interleukin-1 beta (IL-1 beta) and its receptor antagonist (IL-1RA) in 70 EOP patients, including a subgroup of 21 localised EOP (L-EOP) patients and 72 periodontally healthy controls. All subjects were of Caucasian heritage and systemically healthy. A single nucleotide polymorphism (SNP) in exon 5 of the IL-1 beta gene (IL-1 beta+ 3953) was analysed by amplifying the polymorphic region using PCR, followed by restriction digestion with Taq1 and gel electrophoresis.

Results: The frequency of IL-1 beta genotypes homozygous for allele 1 (corresponding to the presence of a restriction site) of the IL-1 beta+3953 SNP was found to be significantly increased in EOP patients (chi2 test, p = 0.025). Upon stratification for smoking status a significant difference was found in the IL-1 beta genotype distribution between EOP smokers compared to control smokers (F-exact test, p = 0.02), but not between EOP non-smokers and control non-smokers. The IL-1 beta 1/1 genotype occurred at a higher frequency in EOP smokers (odds ratio = 4.9) compared to control smokers. A variable number tandem repeat polymorphism (VNTR) in intron 2 of the IL-IRA gene was analysed by amplifying the polymorphic region using PCR and fragment size analysis by gel electrophoresis. There was no evidence for an association of an IL-1RA genotype with EOP. However the combination of IL-1 beta allele 1 and IL-IRA allele 1 (corresponding to 4 repeats) was associated with EOP (Clump, p = 0.01).

Conclusions: These findings suggest that an IL-1 beta genotype in combination with smoking, and a combined IL-1 beta and IL-1RA genotype are risk factors for EOP and support a role for genetic and environmental factors in susceptibility to EOP.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Base Sequence
  • DNA / genetics
  • DNA Primers
  • Female
  • Genotype
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Periodontitis / genetics*
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic / genetics*
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Sialoglycoproteins / genetics

Substances

  • DNA Primers
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • DNA