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

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‐1β (IL‐1β) 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‐1β gene (IL‐1β⁺³⁹⁵³) was analysed by amplifying the polymorphic region using PCR, followed by restriction digestion with Taq1 and gel electrophoresis. Results: The frequency of IL‐1β genotypes homozygous for allele 1 (corresponding to the presence of a restriction site) of the IL‐1β⁺³⁹⁵³ SNP was found to be significantly increased in EOP patients (χ² test, p=0.025). Upon stratification for smoking status a significant difference was found in the IL‐1β 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‐1β 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‐1RA 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‐1β allele 1 and IL‐1RA allele 1 (corresponding to 4 repeats) was associated with EOP (Clump, p=0.01). Conclusions: These findings suggest that an IL‐1β genotype in combination with smoking, and a combined IL‐1β and IL‐1RA genotype are risk factors for EOP and support a role for genetic and environmental factors in susceptibility to EOP.