Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1 alpha protein in gingival crevicular fluid of teeth with severe periodontal disease

Interleukin-1 (IL-1) is a potent stimulator of bone resorption and is stron gly implicated in the destruction due to bystander damage seen in periodont al disease. Recent studies suggest that polymorphisms of the (IL-1) gene co mplex may be significant risk factors for a number of chronic inflammatory diseases. The severity of periodontal disease has been positively associate d with carriage or allele 2 at position -889 of the IL-1A gene in conjuncti on with allele 2 of the IL-1B gene at position +3953. In this study, we tes ted the hypothesis that allele 2 of the IL-1A gene at position -889 might a ct to elevate levels of IL-1 alpha protein in patients with periodontal dis ease. Since levels of IL-1 alpha protein are low in healthy individuals, we used a group of patients with severe periodontal disease to investigate if levels of IL-1 alpha protein in gingival crevicular fluid can be correlate d to patient genotype. IL-1 alpha levels were measured by enzyme immunoassa y in 46 patients with severe periodontal disease. These patients were genot yped by PCP, and allele-specific restriction digests. The carriage rare for allele 2 in the diseased population was 68%. Overall, the carriage of alle le 2 was associated with almost a four-fold increase in IL-1a protein level s. Differences were most pronounced in nonsmokers, while heavy smokers show ed reduced levels of IL-1 alpha protein regardless of genotype. These resul ts suggest a mechanism whereby this genetic polymorphism acts to modulate I L-1 alpha protein production and may influence the pathogenesis of periodon tal disease by affecting the extent of IL-1-associated bystander damage.