Objectives: Interleukin-1 receptor antagonist (IL-1Ra) gene (IL-1RN) polymorphisin is associated with disease susceptibility and activity in several inflammatory diseases. The aim of this study was to investigate IL-1RN genotype and its associations with different periodontal diseases in a group of Turkish subjects. Design and methods: A total of 293 subjects were included in this study. Genomic DNA was obtained from the peripheral blood of 52 patients with generalized aggressive periodontitis (G-AgP), 51 with chronic periodontitis (CP) and 190 reference subjects. A variable number tandem repeat (VNTR) polymorphism in the second intron of the IL-IRN gene was detected by PCR-based methods. Probing pocket depth, clinical attachment loss, plaque accumulation and bleeding on probing (BOP) were recorded. The data were analyzed by the chi(2) test, logistic regression and Mann-Whitney U test. Results: There were significant differences among the groups in the distribution of IL-1RN genotypes (P = 0.0001) and allele frequencies (P = 0.0001). The frequency of IL-1 RN2 allele 2 positivity was higher in the AgP and CP group than the reference group [odds ratio (OR) 6.654, 95% CI: 3.023-16.648; OR 10.327, 95% CI: 4.758-22.412, respectively]. The percentage of sites with BOP was significantly higher in IL-IRN2+ compared to IL-IRN2-CP patients (P = 0.022). Conclusion: These results suggest that IL-IRN2 allele positivity is associated with periodontal disease in a Turkish population. (c) 2005 The Canadian Society of Clinical Chemists. All rights reserved.