title: Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1alpha protein in gingival crevicular fluid of teeth with severe periodontal disease.
abstract: Interleukin-1 (IL-1) is a potent stimulator of bone resorption and is strongly implicated in the destruction due to bystander damage seen in periodontal disease. Recent studies suggest that polymorphisms of the (IL-1) gene complex may be significant risk factors for a number of chronic inflammatory diseases. The severity of periodontal disease has been positively associated with carriage of allele 2 at position -889 of the IL-1A gene in conjunction with allele 2 of the IL-1B gene at position +3953. In this study, we tested the hypothesis that allele 2 of the IL-1A gene at position -889 might act to elevate levels of IL-1alpha protein in patients with periodontal disease. Since levels of IL-1alpha protein are low in healthy individuals, we used a group of patients with severe periodontal disease to investigate if levels of IL-1alpha protein in gingival crevicular fluid can be correlated to patient genotype. IL-1alpha levels were measured by enzyme immunoassay in 46 patients with severe periodontal disease. These patients were genotyped by PCR and allele-specific restriction digests. The carriage rate for allele 2 in the diseased population was 68%. Overall, the carriage of allele 2 was associated with almost a four-fold increase in IL-1alpha protein levels. Differences were most pronounced in non-smokers, while heavy smokers showed reduced levels of IL-1alpha protein regardless of genotype. These results suggest a mechanism whereby this genetic polymorphism acts to modulate IL-1alpha protein production and may influence the pathogenesis of periodontal disease by affecting the extent of IL-1-associated bystander damage.
authors.affiliation: Department of Adult  Oral Health, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Shirodaria
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: I J
authors.initials: IJ
authors.lastname: McKay
authors.forename: C N
authors.initials: CN
authors.lastname: Kennett
authors.forename: F J
authors.initials: FJ
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005883:Gingival Crevicular Fluid / Q000737:chemistry*; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010510:Periodontal Diseases / Q000235:genetics* / Q000378:metabolism; D010512:Periodontal Index; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking; D018709:Statistics, Nonparametric
chemical_list: D007375:Interleukin-1